Genetic factors associated with inhibitor development in hemophilia a

ABSTRACT

The present invention provides methods for predicting the risk of an individual developing antibodies to factor VIII by identifying a single nucleotide polymorphism of an immune response or immune modifier gene. The invention further provides oligonucleotides, diagnostic kits, microarrays, and isolated nucleic acids comprising single nucleotide polymorphisms of immune response or immune modifier genes.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application claims the benefit of U.S. ProvisionalApplication No. 61/326,602, filed Apr. 21, 2010, which is expresslyincorporated herein by reference in its entirety for all purposes.

STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSOREDRESEARCH AND DEVELOPMENT

NOT APPLICABLE

REFERENCE TO A “SEQUENCE LISTING,” A TABLE, OR A COMPUTER PROGRAMLISTING APPENDIX SUBMITTED ON A COMPACT DISK

NOT APPLICABLE

BACKGROUND OF THE INVENTION

Blood coagulation is a complex and dynamic biological process thatdepends on a series of interdependent biochemical reactions. Coagulationfactor VIII (FVIII) is a key component of the blood coagulation cascade.When a bleed occurs, FVIII is directed to the bleeding site and forms aXase complex with activated factor IX (FIXa) and factor X (FX). The Xasecomplex activates FX, which in turn activates prothrombin to thrombin,which activates other components in the coagulation cascade to generatea stable clot (reviewed in Saenko et al., Trends Cardiovasc. Med.,9:185-192 (1999); Lenting et al., Blood, 92:3983-3996 (1998)). Inhemophilia A, a congenital X-linked bleeding disorder characterized by adeficiency in FVIII, the lack of functional FVIII hampers this positivefeedback loop, resulting in incomplete coagulation, which manifests asbleeding episodes of increased duration rather than increased intensity(Zhang et al., Clinic. Rev. Allerg. Immunol., 37:114-124 (2009)).

The severity of hemophilia A varies based on the nature of any mutationto FVIII and the extent of function of any endogenous FVIII that isformed. About two thirds of patients have “severe” hemophilia,characterized as less than 1% functional FVIII. Patients with “moderate”hemophilia have about 1-5% functional FVIII, and patients with “mild”hemophilia have about 5-50% of normal FVIII function (Zhang et al.,Clinic. Rev. Allerg. Immunol., 37:114-124 (2009)). Current treatment forhemophilia typically consists of factor VIII replacement therapy, inwhich the patient receives recombinant or plasma-derived factor VIII toprevent or treat bleeding episodes. However, in approximately 25-30% ofpatients with severe hemophilia A and in approximately 5% of patientswith mild to moderate hemophilia A, inhibitory alloantibodies areproduced against FVIII, abrogating the effectiveness of this treatment(Oldenburg and Pavlova, Haemophilia, 12 (suppl. 6):15-22 (2006)).

Inhibitor development is considered to be the most significantcomplication in the treatment of hemophilia. Patients with inhibitorshave a higher mortality rate because their bleeding episodes become moredifficult and costly to treat, and preventative treatment is generallynot possible in these patients. In patients with high-titer inhibitors,there is an increased risk of developing recurrent bleeding inparticular joints, which may ultimately result in decreased quality oflife, disability, or death from excessive blood loss (Zhang et al.,Clinic. Rev. Allerg. Immunol., 37:114-124 (2009); Gouw and van den Berg,Semin. Thromb. Hemost., 35:723-734 (2009)). Although in some casesimmune tolerance induction can eradicate FVIII inhibitors in patientswith hemophilia A, relapse is possible and not all patients reach immunetolerance (Wight et al., Haemophilia, 9:436-463 (2003)).

Accordingly, there is a need in the art for the identification ofgenetic markers that are associated with increased likelihood ofdeveloping inhibitory antibodies to FVIII and for corresponding methodsof identifying the presence of these genetic markers in hemophiliacpatients. Prior or early identification of such genetic markers couldlead to dose and/or timing adjustments and to the use of alternativetherapies to avoid the development of antibodies to FVIII.

BRIEF SUMMARY OF THE INVENTION

In one aspect, the present invention provides a method for predictingthe risk of developing antibodies against Factor VIII (FVIII) in anindividual diagnosed with Hemophilia, the method comprising the stepsof: (a) detecting the presence of at least one single nucleotidepolymorphism (SNP) selected from the group consisting of a SNP listed inTable 1, a SNP listed in Table 2, a SNP listed in Table 3, and a SNPlisted in Table 4, in a biological sample from the individual; and (b)predicting the risk of the individual of developing antibodies to FVIII.In a preferred embodiment, the at least one SNP is selected from thoselisted in Table 3. In another preferred embodiment, the at least one SNPis selected from the group consisting of rs12368829, rs11744216,rs1863993, rs4147385, rs12546235, rs4242389, rs10054825, rs17535213,rs10072056, and rs17725712.

In a second aspect, the present invention provides a method forpredicting the risk of developing antibodies against Factor VIII (FVIII)in an individual diagnosed with severe Hemophilia, the method comprisingthe steps of: (a) detecting the presence of at least one singlenucleotide polymorphism (SNP) selected from the group consisting of aSNP listed in Table 2 and a SNP listed in Table 4, in a biologicalsample from the individual; and (b) predicting the risk of theindividual of developing antibodies to FVIII. In a preferred embodiment,the at least one SNP is selected from those listed in Table 4. Inanother preferred embodiment, the at least one SNP is selected from thegroup consisting of rs12368829, rs4147385, rs11744216, rs1863993,rs17535213, rs10072056, rs10054825, rs12546235, rs4242389, rs2071336,rs414634, rs17725712, rs11773821, rs8005905, and rs9482888.

In a third aspect, the present invention provides a method for assigningtreatment comprising administration of Factor VIII (FVIII) to anindividual diagnosed with Hemophilia, the method comprising the stepsof: (a) detecting the presence of at least one single nucleotidepolymorphism (SNP) selected from the group consisting of a SNP listed inTable 1, a SNP listed in Table 2, a SNP listed in Table 3, and a SNPlisted in Table 4, in a biological sample from the individual; and (b)predicting the risk of the individual of developing antibodies to FVIII,and (c) assigning therapy comprising administration of Factor VIII tothe individual. In a preferred embodiment, the at least one SNP isselected from those listed in Table 3. In another preferred embodiment,the at least one SNP is selected from the group consisting ofrs12368829, rs11744216, rs1863993, rs4147385, rs12546235, rs4242389,rs10054825, rs17535213, rs10072056, and rs17725712.

In a fourth aspect, the present invention provides a method forassigning treatment comprising administration of Factor VIII (FVIII) toan individual diagnosed with severe Hemophilia, the method comprisingthe steps of: (a) detecting the presence of at least one singlenucleotide polymorphism (SNP) selected from the group consisting of aSNP listed in Table 2 and a SNP listed in Table 4, in a biologicalsample from the individual; and (b) predicting the risk of theindividual of developing antibodies to FVIII, and (c) assigning therapycomprising administration of Factor VIII to the individual. In apreferred embodiment, the at least one SNP is selected from those listedin Table 4. In another preferred embodiment, the at least one SNP isselected from the group consisting of rs12368829, rs4147385, rs11744216,rs1863993, rs17535213, rs10072056, rs10054825, rs12546235, rs4242389,rs2071336, rs414634, rs17725712, rs11773821, rs8005905, and rs9482888.

In a fifth aspect, the present invention provides a method for assigningtreatment comprising administration of Factor VIII bypass therapy to anindividual diagnosed with Hemophilia, the method comprising the stepsof: (a) detecting the presence of at least one single nucleotidepolymorphism (SNP) selected from the group consisting of a SNP listed inTable 1, a SNP listed in Table 2, a SNP listed in Table 3, and a SNPlisted in Table 4, in a biological sample from the individual; and (b)predicting the risk of the individual of developing antibodies to FVIII,and (c) assigning therapy comprising administration of Factor VIIIbypass therapy to the individual. In a preferred embodiment, the atleast one SNP is selected from those listed in Table 3. In anotherpreferred embodiment, the at least one SNP is selected from the groupconsisting of rs12368829, rs11744216, rs1863993, rs4147385, rs12546235,rs4242389, rs10054825, rs17535213, rs10072056, and rs17725712.

In a sixth aspect, the present invention provides a method for assigningtreatment comprising administration of Factor VIII bypass therapy to anindividual diagnosed with severe Hemophilia, the method comprising thesteps of: (a) detecting the presence of at least one single nucleotidepolymorphism (SNP) selected from the group consisting of a SNP listed inTable 2 and a SNP listed in Table 4, in a biological sample from theindividual; and (b) predicting the risk of the individual of developingantibodies to FVIII, and (c) assigning therapy comprising administrationof Factor VIII bypass therapy to the individual. In a preferredembodiment, the at least one SNP is selected from those listed in Table4. In another preferred embodiment, the at least one SNP is selectedfrom the group consisting of rs12368829, rs4147385, rs11744216,rs1863993, rs17535213, rs10072056, rs10054825, rs12546235, rs4242389,rs2071336, rs414634, rs17725712, rs11773821, rs8005905, and rs9482888.

In a seventh aspect, the present invention provides a diagnostic kit forpredicting the risk of developing antibodies against Factor VIII (FVIII)in an individual diagnosed with Hemophilia, the kit comprising at leastone oligonucleotide capable of being used to detect at least one singlenucleotide polymorphism (SNP) selected from the group consisting of aSNP listed in Table 1, a SNP listed in Table 2, a SNP listed in Table 3,and a SNP listed in Table 4. In a preferred embodiment, the at least oneSNP is selected from those listed in Table 3. In another preferredembodiment, the at least one SNP is selected from the group consistingof rs12368829, rs11744216, rs1863993, rs4147385, rs12546235, rs4242389,rs10054825, rs17535213, rs10072056, and rs17725712.

In an eighth aspect, the present invention provides a diagnostic kit forpredicting the risk of developing antibodies against Factor VIII (FVIII)in an individual diagnosed with severe Hemophilia, the kit comprising atleast one oligonucleotide capable of being used to detect at least onesingle nucleotide polymorphism (SNP) selected from the group consistingof a SNP listed in Table 2 and a SNP listed in Table 4. In a preferredembodiment, the at least one SNP is selected from those listed in Table4. In another preferred embodiment, the at least one SNP is selectedfrom the group consisting of rs12368829, rs4147385, rs11744216,rs1863993, rs17535213, rs10072056, rs10054825, rs12546235, rs4242389,rs2071336, rs414634, rs17725712, rs11773821, rs8005905, and rs9482888.

In a ninth aspect, the present invention provides a microarray forpredicting the risk of developing antibodies against Factor VIII (FVIII)in an individual diagnosed with Hemophilia, the microarray comprising asupport having a plurality of discrete regions, each discrete regionhaving a nucleic acid fragment spotted thereon, wherein at least onenucleic acid fragment spotted on the support comprises a sequence thatis complementary to a genomic sequence that flanks a single nucleotidepolymorphism (SNP) selected from the group consisting of a SNP listed inTable 1, a SNP listed in Table 2, a SNP listed in Table 3, and a SNPlisted in Table 4. In a preferred embodiment, the at least one SNP isselected from those listed in Table 3. In another preferred embodiment,the at least one SNP is selected from the group consisting ofrs12368829, rs11744216, rs1863993, rs4147385, rs12546235, rs4242389,rs10054825, rs17535213, rs10072056, and rs17725712.

In a tenth aspect, the present invention provides a microarray forpredicting the risk of developing antibodies against Factor VIII (FVIII)in an individual diagnosed with severe Hemophilia, the microarraycomprising a support having a plurality of discrete regions, eachdiscrete region having a nucleic acid fragment spotted thereon, whereinat least one nucleic acid fragment spotted on the support comprises asequence that is complementary to a genomic sequence that flanks asingle nucleotide polymorphism (SNP) selected from the group consistingof a SNP listed in Table 2 and a SNP listed in Table 4. In a preferredembodiment, the at least one SNP is selected from those listed in Table4. In another preferred embodiment, the at least one SNP is selectedfrom the group consisting of rs12368829, rs4147385, rs11744216,rs1863993, rs17535213, rs10072056, rs10054825, rs12546235, rs4242389,rs2071336, rs414634, rs17725712, rs11773821, rs8005905, and rs9482888.

BRIEF DESCRIPTION OF THE DRAWINGS

Table 1. SNPs associated with inhibitor status in the HemophiliaInhibitor Genetics Study (HIGS) Combined Cohort, as determined in thestudy described in Example 1.

Table 2. SNPs associated with inhibitor status in a subgroup ofindividuals with severe hemophilia, as determined in the study describedin Example 1.

Table 3. SNPs associated with inhibitor status in the HemophiliaInhibitor Genetics Study (HIGS) Combined Cohort, as determined in thestudy described in Example 2.

Table 4. SNPs associated with inhibitor status in a subgroup ofindividuals with severe hemophilia, as determined in the study describedin Example 2.

DETAILED DESCRIPTION OF THE INVENTION I. Introduction

The development of inhibitory alloantibodies against factor VIII isintricately connected with an individual's immune response to FVIII. Forthis reason, it has been proposed that risk factors associated withinhibitor development may include genotypes or polymorphisms associatedwith immune and inflammatory response. The immune response to FVIII isbelieved to develop as an immune response to an external antigen: theantigen is recognized and processed by antigen-presenting cells (APCs)into smaller fragments, then presented on the surface of the APCs inassociation with major histocompatibility complex (MHC) class IImolecules, where it can be recognized by CD4+ T cells specific forFVIII, which in turn, in the presence of costimulatory signals, direct Bcells to generate antibodies to FVIII (reviewed in Reding, Haemophilia,12 (Suppl. 6):30-36 (2006)).

Several studies have found a weak association between MLC/humanleukocyte antigen (HLA) class I alleles A3, B7, and C7, and MLC/HLAclass II alleles DQA0102, DQB0602, DR15 and higher risk of inhibitordevelopment, while HLA class I allele C2 and HLA class II allelesDQA0103, DQB0603, and DR13 were weakly associated with a protectiveeffect against inhibitor development (Oldenburg et al., Thromb Haemost,77:238-242 (1997); Hay et al., Thromb Haemost, 77:234-237 (1997)).However, other studies, including the more recent Malmo InternationalBrother Study (MIBS), have not found any associations between HLAgenotype and inhibitor development (Lippert et al., Thromb Haemost,64:564-568 (1990); Astermark et al., Blood, 108:3739-3745 (2006)). Otherstudies have found associations between inhibitor development and asingle nucleotide polymorphism (SNP) in the promoter region of TNFA,encoding the immunomodulatory and pro-inflammatory cytokine tumornecrosis factor α (Astermark et al., Blood, 108:3739-3745 (2006)); a 134bp long variant of a CA repeat microsatellite in the promoter region ofIL10, encoding the anti-inflammatory cytokine interleukin-10 (Astermarket al., Blood, 107:3167-3172 (2006)); and a SNP in the promoter regionof CTLA4, encoding cytotoxic T-lymphocyte associated protein-4, areceptor mainly displayed on activated T-cells (Astermark et al., J.Thromb. Haemost., 5:263-265 (2007)). However, no association was foundbetween inhibitor development and polymorphisms in IL1 beta and IL4,which encode cytokines and which have both been associated with risk ofdeveloping other autoimmune disorders (Astermark et al., Blood,107:3167-3172 (2006)). It is clear that other genetic markersinfluencing the immune response to FVIII remain to be identified.Recently, Pavlova et al. (Pavlova A et al., Haemophilia 2010 May;16(102):107-12) identified a significantly higher frequency of DRB1*16[odds ratio (OR) 10.2, 95% CI: 5.32-19.57, P<0.0001] and DQB1*0502 (OR2.2, 95% CI: 1.12-4.54, P<0.05) HLA class II aleles was observed inpatients with acquired hemophilia A (AH). In contrast, the frequency ofDRB1*15 and DQB1*0602 alleles was found to be decreased in patients withAH corresponding to an OR of 0.4 for both HLA loci.

The present invention relates to the discovery that SNPs in multipleother immune response, immune modulator, and inflammatory response genesare associated with inhibitor development in hemophiliac patients. Inthe present invention, a combined cohort of three study populations, theHemophilia Inhibitor Genetics Study (HIGS), the Malmo InternationalBrother Study (MIBS), and the Hemophilia Growth and Development Study(HGDS), was formed to conduct an association study to test thehypothesis that antibody development to FVIII is mediated by immuneresponse and immune modifier genes. It was discovered that out of 14,626SNPs from 1,081 genes including cytokines and their receptors,chemokines and their receptors, pathway genes involved in inflammatoryand immune responses, and HLA genes, 329 SNPs were associated with FVIIIinhibitor status. The 329 SNPs of the present invention are describedherein, e.g. in Tables 1, 2, 3, and 4. The SNPs described herein can beused to predict the risk of an individual developing antibodies toFVIII. Predicting whether an individual is at risk of developingantibodies to FVIII, whether it is prior to the individual receivingFVIII therapy or once the individual has begun receiving FVIII therapy,is important because such a prediction makes it possible to adjust thedosage and/or timing of FVIII therapy provided to the individual, or toprovide or adjust an alternative therapy such as bypass therapy, inorder to avoid the individual developing antibodies to FVIII.

The present invention also relates to the discovery of strong SNPassociations between inhibitor development and six markers within fivegenes. It was discovered that in the combined cohort, strong SNPassociations with FVIII inhibitor status for the total group wereobserved in the DOCK2, MAPK9, F13A1, CD36, and PTPRR genes. A strong SNPassociation was found for the SNP rs11744216, a C>G variant in anintronic region of the DOCK2 gene (odds ratio or “OR” of 0.28 and ap-value or “p” of 0.00004); for the SNP rs1863993, a C>T variant in anintronic region of the DOCK2 gene (OR 3.9, p=0.0002); for the SNPrs4147385, a C>T variant in an intronic region of the MAPK9 gene (OR2.0, p=0.0003); for the SNP rs13206518, a T>C variant in an intronicregion of the F13A1 gene (OR 0.32, p=0.00007); for the SNP rs3211834, aA>C variant in an intronic region of the CD36 gene (OR 0.56, p=0.0002);and for the SNP rs1567748, a A>C variant in an intronic region of thePTPRR gene (OR 0.51, p=0.0003).

The six SNPs that were discovered to be strongly associated withinhibitor status are significant because they are located in genes thatare implicated in processes of immune and/or inflammatory responseand/or modulation. In some instances, the genes of the present inventionare implicated in T cell development and/or T cell responsiveness.DOCK2, or Dedicator of cytokinesis 2, is specifically expressed inhematopoietic cells. It has been shown that DOCK2 regulates T cellresponsiveness through immunological synapse formation and that DOCK2 isrequired in T cell precursors for the development of natural killer Tcells, which are important for immune regulation and host defenseagainst pathogens (Kunisaki et al., J. Immunol., 176:4640-4645 (2006)).MAPK9, also known as mitogen-activated protein kinase 9, Jun kinase 2,or stress activate protein kinase, is believed to play a key role in Tcell differentiation. For example, mice deficient in Mapk9 exhibitdisruption in CD4+ T cell differentiation, causing selectivepolarization of CD4+ T cells to the Th2 phenotype (Jaeschke et al.,Proc. Natl. Acad. Sci. USA, 102:6931-6935 (2005); Rincón and Davis,Immunol. Rev., 228:212-224 (2009)). A balance between Th1 cells (IL-1and IFN-γ secreting cells that induce cellular immune response) and Th2cells (IL-4, IL-5, and IL-10 secreting cells that downregulate theinflammatory activities of Th1) is critical for proper immune response,and in some autoimmune diseases there is a disruption of the Th1/Th2balance. PTPRR, or protein tyrosine phosphatase receptor type R, is asignaling molecule that has been found to regulate MAP kinase activity,and therefore may also be implicated in regulating T celldifferentiation by regulating MAPK9 activity.

In some instances, the genes described herein are implicated ininflammatory response. CD36, or cluster of differentiation 36, is aclass B scavenger receptor that has been shown to regulate inflammatorysignaling. For example, f3-amyloid, a peptide associated withAlzheimer's disease, initiates a CD36-dependent pro-inflammatorysignaling cascade in mononuclear cells (Moore et al., J. Biol. Chem.,277:47373-47379 (2002)), and CD36 is required a β-amyloid-induced CD36upregulation of the inflammatory cytokine IL-10 (El Khoury et al., J.Exp. Med., 197:1657-1666 (2003)).

In some instances, the genes described herein are implicated in theblood coagulation cascade. F13A1 encodes coagulation factor XIII (FXIII)A subunit. Upon FXIII activation by thrombin, activated FXIII acts onfibrin to form crosslinks between fibrin molecules as the final step inblood clot formation. SNPs in F13A1 have been reported to be associatedwith other aspects blood coagulation, specifically plasma fibrinogenconcentration and fibrin clot porosity (Mannila et al., Thromb.Haemost., 95:420-427 (2006)).

The present invention also relates to the discovery of strong SNPassociations between inhibitor development in patients with severehemophilia and four markers within three genes. It was discovered thatin the combined cohort, strong SNP associations with FVIII inhibitorstatus for the subgroup with severe hemophilia were observed in theDOCK2, MAPK9, and CD36 genes. For this subgroup, a strong associationwith inhibitor development was found for the SNP rs4147385, a C>Tvariant in an intronic region of the MAPK9 gene (OR 2.3, p=0.00003); forthe SNP rs11744216, a C>G variant in an intronic region of the DOCK2gene (OR 0.30, p=0.00008); for the SNP rs1863993, a C>T variant in anintronic region of the DOCK2 gene (OR 4.4, p=0.0009); and for the SNPrs3211834, a A>C variant in an intronic region of the CD36 gene (OR0.59, p=0.0008).

In one aspect, the present invention provides a method for predictingthe risk of an individual developing antibodies to factor VIII (FVIII),the method comprising the steps of identifying at least one singlenucleotide polymorphism (SNP) selected from the group consisting of theSNPs listed in Table 1, and predicting the risk of the individual ofdeveloping antibodies to FVIII.

In one embodiment, the SNP is located in a gene selected from the groupconsisting of DOCK2, MAPK9, F13A1, CD36, and PTPRR. In one embodiment,the SNP is selected from the group consisting of rs11744216, rs13206518,rs3211834, rs1863993, rs4147385, and rs1567748.

In one embodiment, the method further comprises the steps of amplifyinggenomic DNA of the individual using oligonucleotide primers that amplifythe SNP selected from the group consisting of the SNPS listed in Table1, and identifying the nucleotides present at the SNP.

In one embodiment, the individual has not yet received FVIII therapy. Inone embodiment, the individual has received FVIII therapy. In oneembodiment, the prediction allows for adjusting a dosage of FVIIItherapy received by the individual. In one embodiment, the predictionallows for providing or adjusting a dosage of bypass therapy received bythe individual.

In one embodiment, the individual has severe hemophilia. In oneembodiment, the individual has severe hemophilia and the SNP is locatedin a gene selected from the group consisting of DOCK2, MAPK9, and CD36.In one embodiment, the individual has severe hemophilia and the SNP isselected from the group consisting of rs11744216, rs1863993, rs4147385,and rs3211834.

In one embodiment, the method further comprises the steps of analyzing asample from the individual with an assay that specifically detects theSNP selected from the group consisting of the SNPs listed in Table 1,and identifying the nucleotides present at the SNP. In one embodiment,the assay or step of identification comprises a technique selected fromthe group consisting of mass spectroscopy, RT-PCR, microarrayhybridization, pyrosequencing, thermal cycle sequencing, capillary arraysequencing, and solid phase sequencing. In one embodiment, the assaycomprises microarray hybridization.

In another aspect, the present invention provides an oligonucleotidefrom 10 to 60 nucleotides in length that contacts at least one singlenucleotide polymorphism (SNP) selected from the group consisting of theSNPs listed in Table 1. In one embodiment, the oligonucleotide contactsa SNP located in a gene selected from the group consisting of DOCK2,MAPK9, F13A1, CD36, and PTPRR. In one embodiment, the oligonucleotidecontacts a SNP selected from the group consisting of rs11744216,rs13206518, rs3211834, rs1863993, rs4147385, and rs1567748.

In one embodiment, the oligonucleotide is used to predict the risk of anindividual developing antibodies to factor VIII (FVIII) and to adjust adosage of FVIII therapy received by the individual. In one embodiment,the oligonucleotide is used to provide or adjust a dosage of bypasstherapy received by the individual.

In another aspect, the present invention provides a diagnostic kitcomprising oligonucleotides to detect at least one single nucleotidepolymorphism (SNP) selected from the group consisting of the SNPs listedin Table 1. In one embodiment, the kit comprises oligonucleotides thatdetect a SNP located in a gene selected from the group consisting ofDOCK2, MAPK9, F13A1, CD36, and PTPRR. In one embodiment, the kitcomprises oligonucleotides that detect a SNP selected from the groupconsisting of rs11744216, rs13206518, rs3211834, rs1863993, rs4147385,and rs1567748. In one embodiment, the kit is used to predict the risk ofan individual developing antibodies to factor VIII (FVIII) and to adjusta dosage of FVIII therapy received by the individual. In one embodiment,the kit is used to provide or adjust a dosage of bypass therapy receivedby the individual.

In yet another aspect, the present invention provides a microarraycomprising a support having a plurality of discrete regions, eachdiscrete region having a nucleic acid fragment spotted thereon, whereinthe nucleic acid fragment comprises a sequence that is complementary toa single nucleotide polymorphism (SNP) selected from the groupconsisting of the SNPs listed in Table 1. In one embodiment, themicroarray is used to predict the risk of an individual developingantibodies to factor VIII (FVIII) and to adjust a dosage of FVIIItherapy received by the individual. In one embodiment, the microarray isused to provide or adjust a dosage of bypass therapy received by theindividual.

In still another aspect, the present invention provides an isolatednucleic acid comprising a single nucleotide polymorphism (SNP) selectedfrom the group consisting of the SNPs listed in Table 1. In oneembodiment, the SNP is located in a gene selected from the groupconsisting of DOCK2, MAPK9, F13A1, CD36, and PTPRR. In one embodiment,the SNP is selected from the group consisting of rs11744216, rs13206518,rs3211834, rs1863993, rs4147385, and rs1567748.

The present invention may be understood more readily by reference to thefollowing detailed description of specific embodiments and the Examplesincluded therein.

II. Definitions

As used herein, the following terms have the meanings ascribed to themunless specified otherwise.

As used herein, the term “factor VIII” or “FVIII” refers to any form offactor VIII molecule with the typical characteristics of bloodcoagulation factor VIII, whether derived from blood plasma or producedthrough the use of recombinant DNA techniques, and including allmodified forms of factor. VIII. Factor VIII (FVIII) exists naturally andin therapeutic preparations as a heterogeneous distribution ofpolypeptides arising from a single gene product (see, e.g., Andersson etal., Proc. Nati. Acad. Sci. USA, 83:2979-2983 (1986)). Commerciallyavailable examples of therapeutic preparations containing Factor VIIIinclude those sold under the trade names of HEMOFIL M, ADVATE, andRECOMBINATE (available from Baxter Healthcare Corporation, Deerfield,Ill., U.S.A.).

As used herein, the term “inhibitory antibodies to factor VIII” refersto antibodies that decrease or neutralize the procoagulant function offactor VIII. Inhibitory antibodies to factor VIII may develop inindividuals who are not hemophiliacs, or they may develop in individualswith mild, moderate, or severe hemophilia. An individual may developinhibitory antibodies to factor VIII prior to receiving any factor VIIItherapy, or an individual may develop inhibitory antibodies to factorVIII after the onset of factor VIII therapy. In an individual receivingfactor VIII therapy, inhibitory antibodies to factor VIII often appearearly in the course of therapy, typically after about 9 to 11 exposuredays, but sometimes develop sooner or later than 9 to 11 exposure days,within about 100 exposure days, and may develop at any time after theonset of factor VIII therapy.

As used herein, the term “single nucleotide polymorphism” or “SNP”refers to the occurrence of two or more genetically determinedalternative genotypes in a population. A SNP can occur in a coding (i.e.gene) region of the genome, including the promoter region, untranslated5′ and 3′ regions, introns, and coding regions found in the mRNA, oralternatively can occur in a noncoding region of the genome. In someembodiments, the SNPs associated with gene sequences of the inventionmay be located within 300,000; 200,000; 100,000; 75,000; 50,000; or10,000 base pairs from the gene sequence. SNP analysis is useful fordetecting differences between polynucleotide sequences, such as thesequences identified in Table 1, that are associated with increased riskof developing a disease or condition, such as developing inhibitoryantibodies to FVIII. These polynucleotide sequences may occur in or nearany of the genes listed in Table 1, including for example DOCK2, MAPK9,F13A1, CD36, and PTPRR. The SNPs of the present invention are useful,for instance, for predicting the risk of developing inhibitoryantibodies to FVIII. For example, if an individual carries at least oneSNP linked to a disease-associated allele of the gene sequences of theinvention, the individual is likely at increased risk for developinginhibitory antibodies to FVIII.

It will be understood by the skilled artisan that SNPs may be usedsingly or in combination with other SNPs for any of the uses, e.g.,predicting the risk of developing inhibitory antibodies to FVIII,disclosed herein.

As used herein, the term “gene” refers to the segment of DNA involved inproducing a polypeptide chain; it includes regions preceding andfollowing the coding region, such as the promoter and 3′-untranslatedregion, respectively, as well as intervening sequences (introns) betweenindividual coding segments (exons).

As used herein, the term “oligonucleotide” refers to a nucleic acidsequence of approximately 5 nucleotides or greater in length, and up toas many as approximately 100 nucleotides in length, which can be used asa primer, probe, or amplimer Oligonucleotides are often between about 10and about 50 nucleotides in length, more often between about 10 andabout 40 nucleotides, very often between about 15 and about 30nucleotides, and the terms oligonucleotides or oligomers can also referto synthetic and/or non-naturally occurring nucleic acids (i.e.,comprising nucleic acid analogues or modified backbone residues orlinkages)

As used herein, the term “nucleic acid” refers to deoxyribonucleotidesor ribonucleotides and polymers thereof in either single- ordouble-stranded form, and complements thereof. The term encompassesnucleic acids containing known nucleotide analogs or modified backboneresidues or linkages, which are synthetic, naturally occurring, andnon-naturally occurring, which have similar binding properties as thereference nucleic acid, and which are metabolized in a manner similar tothe reference nucleotides. Examples of such analogs include, withoutlimitation, phosphorothioates, phosphoramidates, methyl phosphonates,chiral-methyl phosphonates, 2-O-methyl ribonucleotides, andpeptide-nucleic acids (PNAs).

For PCR, a temperature of about 36° C. is typical for low stringencyamplification, although annealing temperatures may vary between about32° C. and 48° C. depending on primer length. For high stringency PCRamplification, a temperature of about 62° C. is typical, although highstringency annealing temperatures can range from about 50° C. to about65° C., depending on the primer length and specificity. Typical cycleconditions for both high and low stringency amplifications include adenaturation phase of 90° C.-95° C. for 30 sec-2 min., an annealingphase lasting 30 sec.-2 min., and an extension phase of about 72° C. for1-2 min. Protocols and guidelines for low and high stringencyamplification reactions are provided, e.g., in Innis et al. (1990) PCRProtocols, A Guide to Methods and Applications, Academic Press, Inc.N.Y.).ash conditions can be utilized to provide conditions of similarstringency.

As used herein, the term “sample” includes extractions of nucleic acidsuch as DNA, sections of tissues such as biopsy and autopsy samples, andfrozen sections taken for histological purposes. Such samples includeblood and blood fractions or products (e.g., serum, buffy coat, plasma,platelets, red blood cells, and the like), sputum, cheek cells tissue,cultured cells (e.g., primary cultures, explants, and transformedcells), stool, urine, other biological fluids (e.g., prostatic fluid,gastric fluid, intestinal fluid, renal fluid, lung fluid, cerebrospinalfluid, and the like), etc. A sample is typically obtained from a“subject” such as a eukaryotic organism, most preferably a mammal suchas a primate, e.g., chimpanzee or human; cow; dog; cat; a rodent, e.g.,guinea pig, rat, mouse; rabbit; or a bird; reptile; or fish.

As used herein, the terms “hemophilia” or “haemophilia” refer to a groupof disease states broadly characterized by reduced blood clotting orcoagulation. Hemophilia may refer to Type A, Type B, or Type Chemophilia, or to the composite of all three diseases types. Type Ahemophilia (hemophilia A) is caused by a reduction or loss of factorVIII (FVIII) activity and is the most prominent of the hemophiliasubtypes. Type B hemophilia (hemophilia B) results from the loss orreduction of factor IX (FIX) clotting function. Type C hemophilia(hemophilia C) is a consequence of the loss or reduction in factor XI(FXI) clotting activity. Hemophilia A and B are X-linked diseases, whilehemophilia C is autosomal. Common treatments for hemophilia include bothprophylactic and on-demand administration of clotting factors, such asFVIII, FIX, including Bebulin®-VH, and FXI, as well as FEIBA-VH,desmopressin, and plasma infusions.

As used herein, the term “FVIII therapy” includes any therapeuticapproach of providing factor VIII to a patient to relieve, diminish, orprevent the reoccurrence of one or more symptoms (i.e., clinicalfactors) associated with hemophilia. The term encompasses administeringany compound, drug, procedure, or regimen comprising factor VIII,including any modified form of factor VIII, which is useful formaintaining or improving the health of an individual with hemophilia andincludes any of the therapeutic agents described herein. One skilled inthe art will appreciate that either the course of FVIII therapy or thedose of FVIII therapy can be changed, e.g., based upon the resultsobtained in accordance with the present invention.

As used herein, the term “bypass therapy” includes any therapeuticapproach of providing non-factor VIII hemostatic agents, compounds orcoagulation factors to a patient to relieve, diminish, or prevent thereoccurrence of one or more symptoms (i.e., clinical factors) associatedwith hemophilia. Non-FVIII compounds and coagulation factors that may beprovided include, but are not limited to, Factor VIII Inhibitor BypassActivity (FEIBA), recombinant activated factor VII (FVIIa), prothrombincomplex concentrates, and activated prothrombin complex concentrates.These non-FVIII compounds and coagulation factors may be recombinant orplasma-derived. One skilled in the art will appreciate that either thecourse of bypass therapy or the dose of bypass therapy can be changed,e.g., based upon the results obtained in accordance with the presentinvention.

As used herein, a “combination therapy comprising administration ofFVIII and a FVIII bypass agent” includes any therapeutic approach ofproviding both Factor VIII and a non-Factor VIII hemostatic agent to apatient to relieve, diminish, or prevent the reoccurrence of one or moresymptoms (i.e., clinical factors) associated with hemophilia. The termencompasses administering any compound, drug, procedure, or regimencomprising factor VIII, including any modified form of factor VIII,which is useful for maintaining or improving the health of an individualwith hemophilia and includes any of the therapeutic agents describedherein. Non-FVIII compounds and coagulation factors that may be providedinclude, but are not limited to, Factor VIII Inhibitor Bypass Activity(FEIBA), recombinant activated factor VII (FVIIa), prothrombin complexconcentrates, and activated prothrombin complex concentrates. The FactorVIII and non-Factor VIII compounds and coagulation factors may berecombinant or plasma-derived.

In one embodiment, combination therapy may refer to administration ofFactor VIII and a non-FVIII hemostatic agent in a single therapeuticdose. In another embodiment, combination therapy may refer toadministration of Factor VIII and a non-FVIII hemostatic agent inseparate therapeutic doses. For example, Factor VIII and a non-FVIIIhemostatic agent may be administered in separate doses receivedaccording to a single dosage schedule, or alternatively in separatedoses received according to separate dosing schedules. In oneembodiment, the dosing schedules for the Factor VIII and the non-FVIIIhemostatic agent may be concurrent or alternating (i.e., overlapping).In another embodiments, the dosing schedules may be non-overlapping(i.e., where one dosing regime is completed before beginning a seconddosing regime with the alternate therapy). One skilled in the art willappreciate that either the course and/or dose of FVIII therapy and/ornon-FVIII hemostatic agent (i.e., FVIII bypass agent) can be changed,e.g., based upon the results obtained in accordance with the presentinvention. In one embodiment, the identification of SNPs correspondingto one or more SNPs found in Tables 1 to 4, in a sample from a patientdiagnosed with Hemophilia, will allow one of skill in the art to tailorthe combination therapy (i.e., increase or decrease the regime and/ordose of one or both of the Factor VIII and FVIII bypass agent) to theindividual, based on the individuals risk of developing Factor VIIIinhibitors.

The terms “therapeutically effective amount or dose” or “therapeuticallysufficient amount or dose” or “effective or sufficient amount or dose”refer to a dose that produces therapeutic effects for which it isadministered. For example, a therapeutically effective amount of a druguseful for treating hemophilia can be the amount that is capable ofpreventing or relieving one or more symptoms associated with hemophilia.The exact dose will depend on the purpose of the treatment, and will beascertainable by one skilled in the art using known techniques (see,e.g., Lieberman, Pharmaceutical Dosage Forms (vols. 1-3, 1992); Lloyd,The Art, Science and Technology of Pharmaceutical Compounding (1999);Pickar, Dosage Calculations (1999); and Remington: The Science andPractice of Pharmacy, 20th Edition, 2003, Gennaro, Ed., Lippincott,Williams & Wilkins).

As used herein, an “increased risk” of developing antibodies againstFactor VIII refers to an increased probability or increased likelihoodthat an individual will develop antibodies against Factor VIII, forexample, in response to treatment comprising administration of FactorVIII. In one embodiment, the increased risk is in comparison with anaverage risk of developing Factor VIII inhibitors in a given HemophiliaA population (e.g., the average risk ascribed to an individual for whichSNP genotyping has not been performed. In certain embodiments, anincreased risk will correspond to at least a 5% increased risk. Inanother embodiment, an increased risk will correspond to at least a 10%increased risk. In another embodiment, an increased risk will correspondto at least a 25% increased risk. In another embodiment, an increasedrisk will correspond to at least a 50% increased risk. In anotherembodiment, an increased risk will correspond to at least a 75%increased risk. In another embodiment, an increased risk will correspondto at least a 100% increased risk. In another embodiment, an increasedrisk will correspond to at least a 150% increased risk. In anotherembodiment, an increased risk will correspond to at least a 200%increased risk. In another embodiment, an increased risk will correspondto at least a 250% increased risk. In another embodiment, an increasedrisk will correspond to at least a 300% increased risk. In yet otherembodiments, an increased risk will correspond to at least a 5%increased risk, or at least a 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%,50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 110%, 120%,130%, 140%, 150%, 160%, 170%, 180%, 190%, 200%, 210%, 220%, 230%, 240%,250%, 260%, 270%, 280%, 290%, 300%, 310%, 320%, 330%, 340%, 350%, 360%,370%, 380%, 390%, 400%, 410%, 420%, 430%, 440%, 450%, 460%, 470%, 480%,490%, 500%, 525%, 550%, 575%, 600%, 625%, 650%, 675%, 700%, 750%, 800%,850%, 900%, 950%, 1000%, or greater increased risk.

As used herein, a “decreased risk” of developing antibodies againstFactor VIII refers to a decreased probability or decreased likelihoodthat a individual will develop antibodies against Factor VIII, forexample, in response to treatment comprising administration of FactorVIII. In one embodiment, the decreased risk is in comparison with aaverage risk of developing Factor VIII inhibitors in a given HemophiliaA population (e.g., the average risk ascribed to a individual for whichSNP genotyping has not been performed). In certain embodiments, adecreased risk will correspond to at least a 5% decreased risk. Inanother embodiment, a decreased risk will correspond to at least a 10%decreased risk. In another embodiment, a decreased risk will correspondto at least a 25% decreased risk. In another embodiment, a decreasedrisk will correspond to at least a 50% decreased risk. In anotherembodiment, a decreased risk will correspond to at least a 75% decreasedrisk. In another embodiment, a decreased risk will correspond to atleast a 100% decreased risk. In another embodiment, a decreased riskwill correspond to at least a 150% decreased risk. In anotherembodiment, a decreased risk will correspond to at least a 200%decreased risk. In another embodiment, a decreased risk will correspondto at least a 250% decreased risk. In another embodiment, a decreasedrisk will correspond to at least a 300% decreased risk. In yet otherembodiments, a decreased risk will correspond to at least a 5% decreasedrisk, or at least a 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%,60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 110%, 120%, 130%, 140%,150%, 160%, 170%, 180%, 190%, 200%, 210%, 220%, 230%, 240%, 250%, 260%,270%, 280%, 290%, 300%, 310%, 320%, 330%, 340%, 350%, 360%, 370%, 380%,390%, 400%, 410%, 420%, 430%, 440%, 450%, 460%, 470%, 480%, 490%, 500%,525%, 550%, 575%, 600%, 625%, 650%, 675%, 700%, 750%, 800%, 850%, 900%,950%, 1000%, or greater decreased risk.

III. Predictive Methods and Assays

In certain aspects, the present invention provides methods forpredicting the risk of an individual developing antibodies to factorVIII (FVIII). Risk prediction involves identifying at least one singlenucleotide polymorphism (SNP) selected from the group consisting of theSNPs listed in Table 1, and on the basis of the nucleotides present atthe SNP, determining whether the individual is more likely to developantibodies to FVIII or not. SNP analysis is useful for detectingdifferences between alleles of the polynucleotides (e.g., genes) of theinvention. For example, if an individual carries at least one SNP linkedto a disease or condition-associated allele of the gene sequences of theinvention, the individual is likely at an increased risk of developingantibodies to FVIII. In some embodiments, the SNP associated with thegene sequences of the invention is located within 300,000; 200,000;100,000; 75,000; 50,000; or 10,000 base pairs from the gene sequence.

Predicting the risk of an individual developing antibodies to FVIII maybe performed when the individual has not received any FVIII therapy.Alternatively, risk prediction may be performed soon after theindividual begins receiving FVIII therapy. Alternatively, riskprediction may be performed at any time when there are suspectedsymptoms of FVIII antibody development in the individual. One of skillin the art will be able to identify symptoms of FVIII antibodydevelopment in the individual.

In some embodiments, the present invention provides methods ofpredicting the risk of an individual developing antibodies to FVIIIcomprising identifying a SNP located in a gene selected from the groupconsisting of DOCK2, MAPK9, F13A1, CD36, and PTPRR. In one embodiment,the method comprises identifying the SNP rs11744216 and determiningwhether the individual has a C>G polymorphism that is associated withincreased risk of developing antibodies to FVIII. In one embodiment, themethod comprises identifying the SNP rs13206518 and determining whetherthe individual has a T>C polymorphism that is associated with increasedrisk of developing antibodies to FVIII. In one embodiment, the methodcomprises identifying the SNP rs3211834 and determining whether theindividual has a A>C polymorphism that is associated with increased riskof developing antibodies to FVIII. In one embodiment, the methodcomprises identifying the SNP rs1863993 and determining whether theindividual has a C>T polymorphism that is associated with increased riskof developing antibodies to FVIII. In one embodiment, the methodcomprises identifying the SNP rs4147385 and determining whether theindividual has a C>T polymorphism that is associated with increased riskof developing antibodies to FVIII. In one embodiment, the methodcomprises identifying the SNP rs1567748 and determining whether theindividual has a A>C polymorphism that is associated with increased riskof developing antibodies to FVIII.

The predictive methods of the present invention may also be used todetermine how to provide or adjust a dosage of therapy received by theindividual. In some embodiments, the identification of a variant orcondition-associated genotype for a SNP selected from the SNPs listed inTable 1 allows for adjusting a dosage of FVIII therapy received by theindividual. In some embodiments, the identification of a variant orcondition-associated genotype for a SNP selected from the SNPs listed inTable 1 allows for providing or adjusting a dosage of bypass therapyreceived by the individual.

In some embodiments of the present invention, the individual for whomthe risk prediction is desired may be an individual who has severehemophilia. In some embodiments wherein the individual for whom the riskprediction is desired has severe hemophilia, the SNP to be identifiedmay be located in a gene selected from the group consisting of DOCK2,MAPK9, and CD36 (Table 2). In one embodiment, the individual has severehemophilia and the method comprises identifying the SNP rs11744216 anddetermining whether the individual has a C>G polymorphism that isassociated with increased risk of developing antibodies to FVIII. In oneembodiment, the individual has severe hemophilia and the methodcomprises identifying the SNP rs1863993 and determining whether theindividual has a C>T polymorphism that is associated with increased riskof developing antibodies to FVIII. In one embodiment, the individual hassevere hemophilia and the method comprises identifying the SNP rs4147385and determining whether the individual has a C>T polymorphism that isassociated with increased risk of developing antibodies to FVIII. In oneembodiment, the individual has severe hemophilia and the methodcomprises identifying the SNP rs3211834 and determining whether theindividual has a A>C polymorphism that is associated with increased riskof developing antibodies to FVIII.

The genotype of the SNP of interest in the individual may be measured bytaking a blood, saliva, urine, or other tissue sample containing nucleicacid, e.g., DNA, from the individual and analyzing the sample with anassay that specifically detects the presence of the SNP of interest.Alternatively, the genotype of the SNP of interest in the individual maybe measured by taking a blood, saliva, urine, or other tissue samplefrom the individual and amplifying the genomic DNA of the sample usingoligonucleotide primers that amplify the SNP of interest.

A. Methods for Predicting Risk in Hemophilia Patients

In one aspect, the present invention provides methods for predicting therisk of developing antibodies against Factor VIII (FVIII) in anindividual diagnosed with Hemophilia A by detecting the presence of oneor more of the SNPs identified herein. In one embodiment, the methodcomprises the steps of detecting the presence of at least one singlenucleotide polymorphism (SNP) selected from the group consisting of aSNP listed in Table 1, a SNP listed in Table 2, a SNP listed in Table 3,and a SNP listed in Table 4, in a biological sample from the individual;and predicting the risk of the individual of developing antibodies toFVIII.

Generally, the predicted risk associated with each SNP is relative tothe Odds ratio (OR) calculated for that particular SNP. Therefore, thedetection of a SNP with an OR less than one is generally associated witha reduced likelihood (i.e., a reduced risk) of the individual developingantibodies against Factor VIII. Likewise, the detection of a SNP with anOR greater than one is generally associated with an increased likelihood(i.e., a reduced risk) of the individual developing antibodies againstFactor VIII. Accordingly, treatment can then be assigned and/oradministered to an individual diagnosed with Hemophilia A appropriatelybased on the relative risk of the individual developing antibodiesagainst Factor VIII.

1. Individuals Diagnosed with Hemophilia A

In one embodiment, the present invention provides a method forpredicting the risk of developing antibodies against Factor VIII (FVIII)in an individual diagnosed with Hemophilia A the method comprising thesteps of detecting the presence of at least one single nucleotidepolymorphism (SNP) selected from the group consisting of a SNP listed inTable 1, a SNP listed in Table 2, a SNP listed in Table 3, and a SNPlisted in Table 4, in a biological sample from the individual; andpredicting the risk of the individual of developing antibodies to FVIII.

In one embodiment of the method, the individual has been diagnosed withmild Hemophilia. In another embodiment, the individual has beendiagnosed with moderate Hemophilia. In yet another embodiment, theindividual has been diagnosed with severe Hemophilia.

In one embodiment of the method, the step of detecting the presence ofat least one SNP comprises amplifying a nucleic acid present in thebiological sample. In another embodiment, the step of detecting thepresence of at least one SNP comprises a technique selected from thegroup consisting of mass spectroscopy, RT-PCR, microarray hybridization,pyrosequencing, thermal cycle sequencing, capillary array sequencing,solid phase sequencing, a hybridization-based method, an enzymatic-basedmethod, a PCR-based method, a sequencing method, a ssDNA conformationalmethod, and a DNA melting temperature assay.

In one embodiment, the method further comprises assigning and/oradministering a treatment to the individual based on the predicted riskof developing antibodies against Factor VIII. In a specific embodiment,treatment comprising administration of Factor VIII is assigned to anindividual with a predicted decreased risk of developing antibodiesagainst Factor VIII. In another specific embodiment, treatmentcomprising Factor VIII bypass therapy is assigned to an individual witha predicted increased risk of developing antibodies against Factor VIII.

In yet another specific embodiment, combination therapy comprisingadministration of Factor VIII and a FVIII bypass agent is assigned to anindividual based on the predicted risk of developing antibodies againstFactor VIII. In one specific embodiment, a combination therapy isassigned to an individual with a predicted decreased risk of developingantibodies against Factor VIII. In another specific embodiment, acombination therapy is assigned to an individual with a predictedincreased risk of developing antibodies against Factor VIII.

In one embodiment, treatment comprising administration of Factor VIII isprovided to an individual with a predicted decreased risk of developingantibodies against Factor VIII. In another specific embodiment,treatment comprising Factor VIII bypass therapy is provided to anindividual with a predicted increased risk of developing antibodiesagainst Factor VIII.

In yet another embodiment, combination therapy comprising administrationof Factor VIII and a FVIII bypass agent is provided to an individualbased on the predicted risk of developing antibodies against FactorVIII. In one specific embodiment, a combination therapy is provided toan individual with a predicted decreased risk of developing antibodiesagainst Factor VIII. In another specific embodiment, a combinationtherapy is provided to an individual with a predicted increased risk ofdeveloping antibodies against Factor VIII.

In one embodiment, the method further comprises adjusting a dosage of atreatment comprising administration of Factor VIII to the individualbased on the predicted risk of developing antibodies against FactorVIII. In a specific embodiment, a dosage of Factor VIII to beadministered to an individual with a predicted decreased risk ofdeveloping antibodies against Factor VIII is increased. In anotherspecific embodiment, a dosage of Factor VIII to be administered to anindividual with a predicted increased risk of developing antibodiesagainst Factor VIII is decreased.

In another embodiment, the method further comprises adjusting the dosageand/or frequency of Factor VIII administration in a combination therapybased on the predicted risk of developing antibodies against FVIII. Inone embodiment, the method comprises increasing the dosage or frequencyof Factor VIII administered in a combination therapy to an individualwith a predicted decreased risk of developing antibodies against FactorVIII. In another embodiment, the method comprises decreasing the dosageor frequency of Factor VIII administered in a combination therapy to anindividual with a predicted increased risk of developing antibodiesagainst Factor VIII.

In another embodiment, the method further comprises adjusting the dosageand/or frequency of a non-FVIII hemostatic agent administered in acombination therapy based on the predicted risk of developing antibodiesagainst FVIII. In one embodiment, the method comprises increasing thedosage or frequency of a non-FVIII hemostatic agent administered in acombination therapy to an individual with a predicted increased risk ofdeveloping antibodies against Factor VIII. In another embodiment, themethod comprises decreasing the dosage or frequency of a non-FVIIIhemostatic agent administered in a combination therapy to an individualwith a predicted decreased risk of developing antibodies against FactorVIII.

In another embodiment, the method further comprises adjusting the dosageand/or frequency of both Factor VIII and a non-FVIII hemostatic agentadministered in a combination therapy based on the predicted risk ofdeveloping antibodies against FVIII. In this fashion, a combinationtherapy may be optimized for an individual with a specific predictedrisk of developing antibodies against FVIII. Optimization of the dosageand/or frequency of Factor VIII and non-FVIII hemostatic agents incombination therapy may be achieved by any combination of increasing thefrequency of FVIII administration, decreasing the frequency of FVIIIadministration, increasing the dosage of FVIII, decreasing the dosage ofFVIII, increasing the frequency of non-FVIII hemostatic agentadministration, decreasing the frequency of non-FVIII hemostatic agentadministration, increasing the dosage of a non-FVIII hemostatic agent,and decreasing the dosage of a non-FVIII hemostatic agent.

In a specific embodiment, the method comprises increasing the frequencyand/or dosage of FVIII and decreasing the frequency and/or dosage of anon-FVIII hemostatic agent administered to an individual with apredicted decreased risk of developing antibodies against Factor VIII.

In another specific embodiment, the method comprises decreasing thefrequency and/or dosage of FVIII and increasing the frequency and/ordosage of a non-FVIII hemostatic agent administered to an individualwith a predicted increased risk of developing antibodies against FactorVIII.

In a preferred embodiment, the method comprises the detection of atleast one SNP selected from those listed in Table 3. In a specificembodiment, the method comprises the detection of at least on SNPselected from the group consisting of rs12368829, rs11744216, rs1863993,rs4147385, rs12546235, rs4242389, rs10054825, rs17535213, rs10072056,and rs17725712. In one embodiment, at least one detected SNP isrs12368829. In another embodiment, at least one detected SNP isrs11744216. In another embodiment, at least one detected SNP isrs1863993. In another embodiment, at least one detected SNP isrs4147385. In another embodiment, at least one detected SNP isrs12546235. In another embodiment, at least one detected SNP isrs4242389. In another embodiment, at least one detected SNP isrs10054825. In another embodiment, at least one detected SNP isrs17535213. In another embodiment, at least one detected SNP isrs10072056. In another embodiment, at least one detected SNP isrs17725712.

a) Prior to Factor VIII Therapy

In one embodiment, the present invention relates specifically to anindividual or group of individuals diagnosed with Hemophilia A that havenot previously received Factor VIII therapy (i.e., not receivedtreatment comprising administration of Factor VIII).

In one embodiment, a method is provided for predicting the risk ofdeveloping antibodies against Factor VIII (FVIII) in an individualdiagnosed with Hemophilia A, who has not previously received treatmentcomprising administration of FVIII, comprising detecting the presence ofat least one single nucleotide polymorphism (SNP) selected from thegroup consisting of a SNP listed in Table 1, a SNP listed in Table 2, aSNP listed in Table 3, and a SNP listed in Table 4, in a biologicalsample from the individual; and predicting the risk of the individual ofdeveloping antibodies to FVIII.

In one embodiment of the method, the individual has been diagnosed withmild Hemophilia. In another embodiment, the individual has beendiagnosed with moderate Hemophilia. In yet another embodiment, theindividual has been diagnosed with severe Hemophilia.

In one embodiment of the method, the step of detecting the presence ofat least one SNP comprises amplifying a nucleic acid present in thebiological sample. In another embodiment, the step of detecting thepresence of at least one SNP comprises a technique selected from thegroup consisting of mass spectroscopy, RT-PCR, microarray hybridization,pyrosequencing, thermal cycle sequencing, capillary array sequencing,solid phase sequencing, a hybridization-based method, an enzymatic-basedmethod, a PCR-based method, a sequencing method, a ssDNA conformationalmethod, and a DNA melting temperature assay.

In one embodiment, the method further comprises assigning and/oradministering a treatment to the individual based on the predicted riskof developing antibodies against Factor VIII. In a specific embodiment,treatment comprising administration of Factor VIII is assigned to anindividual with a predicted decreased risk of developing antibodiesagainst Factor VIII. In another specific embodiment, treatmentcomprising Factor VIII bypass therapy is assigned to an individual witha predicted increased risk of developing antibodies against Factor VIII.

In yet another specific embodiment, combination therapy comprisingadministration of Factor VIII and a FVIII bypass agent is assigned to anindividual based on the predicted risk of developing antibodies againstFactor VIII. In one specific embodiment, a combination therapy isassigned to an individual with a predicted decreased risk of developingantibodies against Factor VIII. In another specific embodiment, acombination therapy is assigned to an individual with a predictedincreased risk of developing antibodies against Factor VIII.

In one embodiment, treatment comprising administration of Factor VIII isprovided to an individual with a predicted decreased risk of developingantibodies against Factor VIII. In another specific embodiment,treatment comprising Factor VIII bypass therapy is provided to anindividual with a predicted increased risk of developing antibodiesagainst Factor VIII.

In yet another embodiment, combination therapy comprising administrationof Factor VIII and a FVIII bypass agent is provided to an individualbased on the predicted risk of developing antibodies against FactorVIII. In one specific embodiment, a combination therapy is provided toan individual with a predicted decreased risk of developing antibodiesagainst Factor VIII. In another specific embodiment, a combinationtherapy is provided to an individual with a predicted increased risk ofdeveloping antibodies against Factor VIII.

In one embodiment, the method further comprises adjusting a dosage of atreatment comprising administration of Factor VIII to the individualbased on the predicted risk of developing antibodies against FactorVIII. In a specific embodiment, a dosage of Factor VIII to beadministered to an individual with a predicted decreased risk ofdeveloping antibodies against Factor VIII is increased. In anotherspecific embodiment, a dosage of Factor VIII to be administered to anindividual with a predicted increased risk of developing antibodiesagainst Factor VIII is decreased.

In another embodiment, the method further comprises adjusting the dosageand/or frequency of Factor VIII administration in a combination therapybased on the predicted risk of developing antibodies against FVIII. Inone embodiment, the method comprises increasing the dosage or frequencyof Factor VIII administered in a combination therapy to an individualwith a predicted decreased risk of developing antibodies against FactorVIII. In another embodiment, the method comprises decreasing the dosageor frequency of Factor VIII administered in a combination therapy to anindividual with a predicted increased risk of developing antibodiesagainst Factor VIII.

In another embodiment, the method further comprises adjusting the dosageand/or frequency of a non-FVIII hemostatic agent administered in acombination therapy based on the predicted risk of developing antibodiesagainst FVIII. In one embodiment, the method comprises increasing thedosage or frequency of a non-FVIII hemostatic agent administered in acombination therapy to an individual with a predicted increased risk ofdeveloping antibodies against Factor VIII. In another embodiment, themethod comprises decreasing the dosage or frequency of a non-FVIIIhemostatic agent administered in a combination therapy to an individualwith a predicted decreased risk of developing antibodies against FactorVIII.

In another embodiment, the method further comprises adjusting the dosageand/or frequency of both Factor VIII and a non-FVIII hemostatic agentadministered in a combination therapy based on the predicted risk ofdeveloping antibodies against FVIII. In this fashion, a combinationtherapy may be optimized for an individual with a specific predictedrisk of developing antibodies against FVIII. Optimization of the dosageand/or frequency of Factor VIII and non-FVIII hemostatic agents incombination therapy may be achieved by any combination of increasing thefrequency of FVIII administration, decreasing the frequency of FVIIIadministration, increasing the dosage of FVIII, decreasing the dosage ofFVIII, increasing the frequency of non-FVIII hemostatic agentadministration, decreasing the frequency of non-FVIII hemostatic agentadministration, increasing the dosage of a non-FVIII hemostatic agent,and decreasing the dosage of a non-FVIII hemostatic agent.

In a specific embodiment, the method comprises increasing the frequencyand/or dosage of FVIII and decreasing the frequency and/or dosage of anon-FVIII hemostatic agent administered to an individual with apredicted decreased risk of developing antibodies against Factor VIII.

In another specific embodiment, the method comprises decreasing thefrequency and/or dosage of FVIII and increasing the frequency and/ordosage of a non-FVIII hemostatic agent administered to an individualwith a predicted increased risk of developing antibodies against FactorVIII.

In a preferred embodiment, the method comprises the detection of atleast one SNP selected from those listed in Table 3. In a specificembodiment, the method comprises the detection of at least on SNPselected from the group consisting of rs12368829, rs11744216, rs1863993,rs4147385, rs12546235, rs4242389, rs10054825, rs17535213, rs10072056,and rs17725712. In one embodiment, at least one detected SNP isrs12368829. In another embodiment, at least one detected SNP isrs11744216. In another embodiment, at least one detected SNP isrs1863993. In another embodiment, at least one detected SNP isrs4147385. In another embodiment, at least one detected SNP isrs12546235. In another embodiment, at least one detected SNP isrs4242389. In another embodiment, at least one detected SNP isrs10054825. In another embodiment, at least one detected SNP isrs17535213. In another embodiment, at least one detected SNP isrs10072056. In another embodiment, at least one detected SNP isrs17725712.

b) After Initial Factor VIII Therapy

In one embodiment, the present invention relates specifically to anindividual or group of individuals diagnosed with Hemophilia A that havepreviously received Factor VIII therapy (i.e., received treatmentcomprising administration of Factor VIII).

In one embodiment, a method is provided for predicting the risk ofdeveloping antibodies against Factor VIII (FVIII) in an individualdiagnosed with Hemophilia A, who has previously received treatmentcomprising administration of FVIII, comprising detecting the presence ofat least one single nucleotide polymorphism (SNP) selected from thegroup consisting of a SNP listed in Table 1, a SNP listed in Table 2, aSNP listed in Table 3, and a SNP listed in Table 4, in a biologicalsample from the individual; and predicting the risk of the individual ofdeveloping antibodies to FVIII.

In one embodiment of the method, the individual has been diagnosed withmild Hemophilia. In another embodiment, the individual has beendiagnosed with moderate Hemophilia. In yet another embodiment, theindividual has been diagnosed with severe Hemophilia.

In one embodiment of the method, the step of detecting the presence ofat least one SNP comprises amplifying a nucleic acid present in thebiological sample. In another embodiment, the step of detecting thepresence of at least one SNP comprises a technique selected from thegroup consisting of mass spectroscopy, RT-PCR, microarray hybridization,pyrosequencing, thermal cycle sequencing, capillary array sequencing,solid phase sequencing, a hybridization-based method, an enzymatic-basedmethod, a PCR-based method, a sequencing method, a ssDNA conformationalmethod, and a DNA melting temperature assay.

In one embodiment, the method further comprises assigning and/oradministering a treatment to the individual based on the predicted riskof developing antibodies against Factor VIII. In a specific embodiment,treatment comprising administration of Factor VIII is assigned to anindividual with a predicted decreased risk of developing antibodiesagainst Factor VIII. In another specific embodiment, treatmentcomprising Factor VIII bypass therapy is assigned to an individual witha predicted increased risk of developing antibodies against Factor VIII.

In yet another specific embodiment, combination therapy comprisingadministration of Factor VIII and a FVIII bypass agent is assigned to anindividual based on the predicted risk of developing antibodies againstFactor VIII. In one specific embodiment, a combination therapy isassigned to an individual with a predicted decreased risk of developingantibodies against Factor VIII. In another specific embodiment, acombination therapy is assigned to an individual with a predictedincreased risk of developing antibodies against Factor VIII.

In one embodiment, treatment comprising administration of Factor VIII isprovided to an individual with a predicted decreased risk of developingantibodies against Factor VIII. In another specific embodiment,treatment comprising Factor VIII bypass therapy is provided to anindividual with a predicted increased risk of developing antibodiesagainst Factor VIII.

In yet another embodiment, combination therapy comprising administrationof Factor VIII and a FVIII bypass agent is provided to an individualbased on the predicted risk of developing antibodies against FactorVIII. In one specific embodiment, a combination therapy is provided toan individual with a predicted decreased risk of developing antibodiesagainst Factor VIII. In another specific embodiment, a combinationtherapy is provided to an individual with a predicted increased risk ofdeveloping antibodies against Factor VIII.

In one embodiment, the method further comprises adjusting a dosage of atreatment comprising administration of Factor VIII to the individualbased on the predicted risk of developing antibodies against FactorVIII. In a specific embodiment, a dosage of Factor VIII to beadministered to an individual with a predicted decreased risk ofdeveloping antibodies against Factor VIII is increased. In anotherspecific embodiment, a dosage of Factor VIII to be administered to anindividual with a predicted increased risk of developing antibodiesagainst Factor VIII is decreased.

In another embodiment, the method further comprises adjusting the dosageand/or frequency of Factor VIII administration in a combination therapybased on the predicted risk of developing antibodies against FVIII. Inone embodiment, the method comprises increasing the dosage or frequencyof Factor VIII administered in a combination therapy to an individualwith a predicted decreased risk of developing antibodies against FactorVIII. In another embodiment, the method comprises decreasing the dosageor frequency of Factor VIII administered in a combination therapy to anindividual with a predicted increased risk of developing antibodiesagainst Factor VIII.

In another embodiment, the method further comprises adjusting the dosageand/or frequency of a non-FVIII hemostatic agent administered in acombination therapy based on the predicted risk of developing antibodiesagainst FVIII. In one embodiment, the method comprises increasing thedosage or frequency of a non-FVIII hemostatic agent administered in acombination therapy to an individual with a predicted increased risk ofdeveloping antibodies against Factor VIII. In another embodiment, themethod comprises decreasing the dosage or frequency of a non-FVIIIhemostatic agent administered in a combination therapy to an individualwith a predicted decreased risk of developing antibodies against FactorVIII.

In another embodiment, the method further comprises adjusting the dosageand/or frequency of both Factor VIII and a non-FVIII hemostatic agentadministered in a combination therapy based on the predicted risk ofdeveloping antibodies against FVIII. In this fashion, a combinationtherapy may be optimized for an individual with a specific predictedrisk of developing antibodies against FVIII. Optimization of the dosageand/or frequency of Factor VIII and non-FVIII hemostatic agents incombination therapy may be achieved by any combination of increasing thefrequency of FVIII administration, decreasing the frequency of FVIIIadministration, increasing the dosage of FVIII, decreasing the dosage ofFVIII, increasing the frequency of non-FVIII hemostatic agentadministration, decreasing the frequency of non-FVIII hemostatic agentadministration, increasing the dosage of a non-FVIII hemostatic agent,and decreasing the dosage of a non-FVIII hemostatic agent.

In a specific embodiment, the method comprises increasing the frequencyand/or dosage of FVIII and decreasing the frequency and/or dosage of anon-FVIII hemostatic agent administered to an individual with apredicted decreased risk of developing antibodies against Factor VIII.

In another specific embodiment, the method comprises decreasing thefrequency and/or dosage of FVIII and increasing the frequency and/ordosage of a non-FVIII hemostatic agent administered to an individualwith a predicted increased risk of developing antibodies against FactorVIII.

In a preferred embodiment, the method comprises the detection of atleast one SNP selected from those listed in Table 3. In a specificembodiment, the method comprises the detection of at least on SNPselected from the group consisting of rs12368829, rs11744216, rs1863993,rs4147385, rs12546235, rs4242389, rs10054825, rs17535213, rs10072056,and rs17725712. In one embodiment, at least one detected SNP isrs12368829. In another embodiment, at least one detected SNP isrs11744216. In another embodiment, at least one detected SNP isrs1863993. In another embodiment, at least one detected SNP isrs4147385. In another embodiment, at least one detected SNP isrs12546235. In another embodiment, at least one detected SNP isrs4242389. In another embodiment, at least one detected SNP isrs10054825. In another embodiment, at least one detected SNP isrs17535213. In another embodiment, at least one detected SNP isrs10072056. In another embodiment, at least one detected SNP isrs17725712.

2. Individuals Diagnosed with Severe Hemophilia A

In one embodiment, the present invention provides a method forpredicting the risk of developing antibodies against Factor VIII (FVIII)in an individual diagnosed with severe Hemophilia A, the methodcomprising the steps of detecting the presence of at least one singlenucleotide polymorphism (SNP) selected from the group consisting of aSNP listed in Table 2 and a SNP listed in Table 4, in a biologicalsample from the individual; and predicting the risk of the individual ofdeveloping antibodies to FVIII.

In one embodiment of the method, the step of detecting the presence ofat least one SNP comprises amplifying a nucleic acid present in thebiological sample. In another embodiment, the step of detecting thepresence of at least one SNP comprises a technique selected from thegroup consisting of mass spectroscopy, RT-PCR, microarray hybridization,pyrosequencing, thermal cycle sequencing, capillary array sequencing,solid phase sequencing, a hybridization-based method, an enzymatic-basedmethod, a PCR-based method, a sequencing method, a ssDNA conformationalmethod, and a DNA melting temperature assay.

In one embodiment, the method further comprises assigning and/oradministering a treatment to the individual based on the predicted riskof developing antibodies against Factor VIII. In a specific embodiment,treatment comprising administration of Factor VIII is assigned to anindividual with a predicted decreased risk of developing antibodiesagainst Factor VIII. In another specific embodiment, treatmentcomprising Factor VIII bypass therapy is assigned to an individual witha predicted increased risk of developing antibodies against Factor VIII.

In yet another specific embodiment, combination therapy comprisingadministration of Factor VIII and a FVIII bypass agent is assigned to anindividual based on the predicted risk of developing antibodies againstFactor VIII. In one specific embodiment, a combination therapy isassigned to an individual with a predicted decreased risk of developingantibodies against Factor VIII. In another specific embodiment, acombination therapy is assigned to an individual with a predictedincreased risk of developing antibodies against Factor VIII.

In one embodiment, treatment comprising administration of Factor VIII isprovided to an individual with a predicted decreased risk of developingantibodies against Factor VIII. In another specific embodiment,treatment comprising Factor VIII bypass therapy is provided to anindividual with a predicted increased risk of developing antibodiesagainst Factor VIII.

In yet another embodiment, combination therapy comprising administrationof Factor VIII and a FVIII bypass agent is provided to an individualbased on the predicted risk of developing antibodies against FactorVIII. In one specific embodiment, a combination therapy is provided toan individual with a predicted decreased risk of developing antibodiesagainst Factor VIII. In another specific embodiment, a combinationtherapy is provided to an individual with a predicted increased risk ofdeveloping antibodies against Factor VIII.

In one embodiment, the method further comprises adjusting a dosage of atreatment comprising administration of Factor VIII to the individualbased on the predicted risk of developing antibodies against FactorVIII. In a specific embodiment, a dosage of Factor VIII to beadministered to an individual with a predicted decreased risk ofdeveloping antibodies against Factor VIII is increased. In anotherspecific embodiment, a dosage of Factor VIII to be administered to anindividual with a predicted increased risk of developing antibodiesagainst Factor VIII is decreased.

In another embodiment, the method further comprises adjusting the dosageand/or frequency of Factor VIII administration in a combination therapybased on the predicted risk of developing antibodies against FVIII. Inone embodiment, the method comprises increasing the dosage or frequencyof Factor VIII administered in a combination therapy to an individualwith a predicted decreased risk of developing antibodies against FactorVIII. In another embodiment, the method comprises decreasing the dosageor frequency of Factor VIII administered in a combination therapy to anindividual with a predicted increased risk of developing antibodiesagainst Factor VIII.

In another embodiment, the method further comprises adjusting the dosageand/or frequency of a non-FVIII hemostatic agent administered in acombination therapy based on the predicted risk of developing antibodiesagainst FVIII. In one embodiment, the method comprises increasing thedosage or frequency of a non-FVIII hemostatic agent administered in acombination therapy to an individual with a predicted increased risk ofdeveloping antibodies against Factor VIII. In another embodiment, themethod comprises decreasing the dosage or frequency of a non-FVIIIhemostatic agent administered in a combination therapy to an individualwith a predicted decreased risk of developing antibodies against FactorVIII.

In another embodiment, the method further comprises adjusting the dosageand/or frequency of both Factor VIII and a non-FVIII hemostatic agentadministered in a combination therapy based on the predicted risk ofdeveloping antibodies against FVIII. In this fashion, a combinationtherapy may be optimized for an individual with a specific predictedrisk of developing antibodies against FVIII. Optimization of the dosageand/or frequency of Factor VIII and non-FVIII hemostatic agents incombination therapy may be achieved by any combination of increasing thefrequency of FVIII administration, decreasing the frequency of FVIIIadministration, increasing the dosage of FVIII, decreasing the dosage ofFVIII, increasing the frequency of non-FVIII hemostatic agentadministration, decreasing the frequency of non-FVIII hemostatic agentadministration, increasing the dosage of a non-FVIII hemostatic agent,and decreasing the dosage of a non-FVIII hemostatic agent.

In a specific embodiment, the method comprises increasing the frequencyand/or dosage of FVIII and decreasing the frequency and/or dosage of anon-FVIII hemostatic agent administered to an individual with apredicted decreased risk of developing antibodies against Factor VIII.

In another specific embodiment, the method comprises decreasing thefrequency and/or dosage of FVIII and increasing the frequency and/ordosage of a non-FVIII hemostatic agent administered to an individualwith a predicted increased risk of developing antibodies against FactorVIII.

In a preferred embodiment, the method comprises the detection of atleast one SNP selected from those listed in Table 4. In a specificembodiment, the method comprises the detection of at least on SNPselected from the group consisting of rs12368829, rs4147385, rs11744216,rs1863993, rs17535213, rs10072056, rs10054825, rs12546235, rs4242389,rs2071336, rs414634, rs17725712, rs11773821, rs8005905, and rs9482888.In one embodiment, at least one detected SNP is rs12368829. In anotherembodiment, at least one detected SNP is rs4147385. In anotherembodiment, at least one detected SNP is rs11744216. In anotherembodiment, at least one detected SNP is rs1863993. In anotherembodiment, at least one detected SNP is rs17535213. In anotherembodiment, at least one detected SNP is rs10072056.

In another embodiment, at least one detected SNP is rs10054825. Inanother embodiment, at least one detected SNP is rs12546235. In anotherembodiment, at least one detected SNP is rs4242389. In anotherembodiment, at least one detected SNP is rs2071336. In anotherembodiment, at least one detected SNP is rs414634. In anotherembodiment, at least one detected SNP is rs17725712. In anotherembodiment, at least one detected SNP is rs11773821.

In another embodiment, at least one detected SNP is rs8005905. Inanother embodiment, at least one detected SNP is rs9482888.

a) Prior to Factor VIII Therapy

In one embodiment, the present invention relates specifically to anindividual or group of individuals diagnosed with severe Hemophilia Athat have not previously received Factor VIII therapy (i.e., notreceived treatment comprising administration of Factor VIII).

In one embodiment, a method is provided for predicting the risk ofdeveloping antibodies against Factor VIII (FVIII) in an individualdiagnosed with severe Hemophilia A, who has not previously receivedtreatment comprising administration of FVIII, comprising detecting thepresence of at least one single nucleotide polymorphism (SNP) selectedfrom the group consisting of a SNP listed in Table 2 and a SNP listed inTable 4, in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII.

In one embodiment of the method, the individual has been diagnosed withmild Hemophilia. In another embodiment, the individual has beendiagnosed with moderate Hemophilia. In yet another embodiment, theindividual has been diagnosed with severe Hemophilia.

In one embodiment of the method, the step of detecting the presence ofat least one SNP comprises amplifying a nucleic acid present in thebiological sample. In another embodiment, the step of detecting thepresence of at least one SNP comprises a technique selected from thegroup consisting of mass spectroscopy, RT-PCR, microarray hybridization,pyrosequencing, thermal cycle sequencing, capillary array sequencing,solid phase sequencing, a hybridization-based method, an enzymatic-basedmethod, a PCR-based method, a sequencing method, a ssDNA conformationalmethod, and a DNA melting temperature assay.

In one embodiment, the method further comprises assigning and/oradministering a treatment to the individual based on the predicted riskof developing antibodies against Factor VIII. In a specific embodiment,treatment comprising administration of Factor VIII is assigned to anindividual with a predicted decreased risk of developing antibodiesagainst Factor VIII. In another specific embodiment, treatmentcomprising Factor VIII bypass therapy is assigned to an individual witha predicted increased risk of developing antibodies against Factor VIII.

In yet another specific embodiment, combination therapy comprisingadministration of Factor VIII and a FVIII bypass agent is assigned to anindividual based on the predicted risk of developing antibodies againstFactor VIII. In one specific embodiment, a combination therapy isassigned to an individual with a predicted decreased risk of developingantibodies against Factor VIII. In another specific embodiment, acombination therapy is assigned to an individual with a predictedincreased risk of developing antibodies against Factor VIII.

In one embodiment, treatment comprising administration of Factor VIII isprovided to an individual with a predicted decreased risk of developingantibodies against Factor VIII. In another specific embodiment,treatment comprising Factor VIII bypass therapy is provided to anindividual with a predicted increased risk of developing antibodiesagainst Factor VIII.

In yet another embodiment, combination therapy comprising administrationof Factor VIII and a FVIII bypass agent is provided to an individualbased on the predicted risk of developing antibodies against FactorVIII. In one specific embodiment, a combination therapy is provided toan individual with a predicted decreased risk of developing antibodiesagainst Factor VIII. In another specific embodiment, a combinationtherapy is provided to an individual with a predicted increased risk ofdeveloping antibodies against Factor VIII.

In one embodiment, the method further comprises adjusting a dosage of atreatment comprising administration of Factor VIII to the individualbased on the predicted risk of developing antibodies against FactorVIII. In a specific embodiment, a dosage of Factor VIII to beadministered to an individual with a predicted decreased risk ofdeveloping antibodies against Factor VIII is increased. In anotherspecific embodiment, a dosage of Factor VIII to be administered to anindividual with a predicted increased risk of developing antibodiesagainst Factor VIII is decreased.

In another embodiment, the method further comprises adjusting the dosageand/or frequency of Factor VIII administration in a combination therapybased on the predicted risk of developing antibodies against FVIII. Inone embodiment, the method comprises increasing the dosage or frequencyof Factor VIII administered in a combination therapy to an individualwith a predicted decreased risk of developing antibodies against FactorVIII. In another embodiment, the method comprises decreasing the dosageor frequency of Factor VIII administered in a combination therapy to anindividual with a predicted increased risk of developing antibodiesagainst Factor VIII.

In another embodiment, the method further comprises adjusting the dosageand/or frequency of a non-FVIII hemostatic agent administered in acombination therapy based on the predicted risk of developing antibodiesagainst FVIII. In one embodiment, the method comprises increasing thedosage or frequency of a non-FVIII hemostatic agent administered in acombination therapy to an individual with a predicted increased risk ofdeveloping antibodies against Factor VIII. In another embodiment, themethod comprises decreasing the dosage or frequency of a non-FVIIIhemostatic agent administered in a combination therapy to an individualwith a predicted decreased risk of developing antibodies against FactorVIII.

In another embodiment, the method further comprises adjusting the dosageand/or frequency of both Factor VIII and a non-FVIII hemostatic agentadministered in a combination therapy based on the predicted risk ofdeveloping antibodies against FVIII. In this fashion, a combinationtherapy may be optimized for an individual with a specific predictedrisk of developing antibodies against FVIII. Optimization of the dosageand/or frequency of Factor VIII and non-FVIII hemostatic agents incombination therapy may be achieved by any combination of increasing thefrequency of FVIII administration, decreasing the frequency of FVIIIadministration, increasing the dosage of FVIII, decreasing the dosage ofFVIII, increasing the frequency of non-FVIII hemostatic agentadministration, decreasing the frequency of non-FVIII hemostatic agentadministration, increasing the dosage of a non-FVIII hemostatic agent,and decreasing the dosage of a non-FVIII hemostatic agent.

In a specific embodiment, the method comprises increasing the frequencyand/or dosage of FVIII and decreasing the frequency and/or dosage of anon-FVIII hemostatic agent administered to an individual with apredicted decreased risk of developing antibodies against Factor VIII.

In another specific embodiment, the method comprises decreasing thefrequency and/or dosage of FVIII and increasing the frequency and/ordosage of a non-FVIII hemostatic agent administered to an individualwith a predicted increased risk of developing antibodies against FactorVIII.

In a preferred embodiment, the method comprises the detection of atleast one SNP selected from those listed in Table 4. In a specificembodiment, the method comprises the detection of at least on SNPselected from the group consisting of rs12368829, rs4147385, rs11744216,rs1863993, rs17535213, rs10072056, rs10054825, rs12546235, rs4242389,rs2071336, rs414634, rs17725712, rs11773821, rs8005905, and rs9482888.In one embodiment, at least one detected SNP is rs12368829. In anotherembodiment, at least one detected SNP is rs4147385. In anotherembodiment, at least one detected SNP is rs11744216. In anotherembodiment, at least one detected SNP is rs1863993. In anotherembodiment, at least one detected SNP is rs17535213. In anotherembodiment, at least one detected SNP is rs10072056.

In another embodiment, at least one detected SNP is rs10054825. Inanother embodiment, at least one detected SNP is rs12546235. In anotherembodiment, at least one detected SNP is rs4242389. In anotherembodiment, at least one detected SNP is rs2071336. In anotherembodiment, at least one detected SNP is rs414634. In anotherembodiment, at least one detected SNP is rs17725712. In anotherembodiment, at least one detected SNP is rs11773821.

In another embodiment, at least one detected SNP is rs8005905. Inanother embodiment, at least one detected SNP is rs9482888.

b) After Initial Factor VIII Therapy

In one embodiment, the present invention relates specifically to anindividual or group of individuals diagnosed with severe Hemophilia Athat have previously received Factor VIII therapy (i.e., receivedtreatment comprising administration of Factor VIII).

In one embodiment, a method is provided for predicting the risk ofdeveloping antibodies against Factor VIII (FVIII) in an individualdiagnosed with severe Hemophilia A, who has previously receivedtreatment comprising administration of FVIII, comprising detecting thepresence of at least one single nucleotide polymorphism (SNP) selectedfrom the group consisting of a SNP listed in Table 2 and a SNP listed inTable 4, in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII.

In one embodiment of the method, the individual has been diagnosed withmild Hemophilia. In another embodiment, the individual has beendiagnosed with moderate Hemophilia. In yet another embodiment, theindividual has been diagnosed with severe Hemophilia.

In one embodiment of the method, the step of detecting the presence ofat least one SNP comprises amplifying a nucleic acid present in thebiological sample. In another embodiment, the step of detecting thepresence of at least one SNP comprises a technique selected from thegroup consisting of mass spectroscopy, RT-PCR, microarray hybridization,pyrosequencing, thermal cycle sequencing, capillary array sequencing,solid phase sequencing, a hybridization-based method, an enzymatic-basedmethod, a PCR-based method, a sequencing method, a ssDNA conformationalmethod, and a DNA melting temperature assay.

In one embodiment, the method further comprises assigning and/oradministering a treatment to the individual based on the predicted riskof developing antibodies against Factor VIII. In a specific embodiment,treatment comprising administration of Factor VIII is assigned to anindividual with a predicted decreased risk of developing antibodiesagainst Factor VIII. In another specific embodiment, treatmentcomprising Factor VIII bypass therapy is assigned to an individual witha predicted increased risk of developing antibodies against Factor VIII.

In yet another specific embodiment, combination therapy comprisingadministration of Factor VIII and a FVIII bypass agent is assigned to anindividual based on the predicted risk of developing antibodies againstFactor VIII. In one specific embodiment, a combination therapy isassigned to an individual with a predicted decreased risk of developingantibodies against Factor VIII. In another specific embodiment, acombination therapy is assigned to an individual with a predictedincreased risk of developing antibodies against Factor VIII.

In one embodiment, treatment comprising administration of Factor VIII isprovided to an individual with a predicted decreased risk of developingantibodies against Factor VIII. In another specific embodiment,treatment comprising Factor VIII bypass therapy is provided to anindividual with a predicted increased risk of developing antibodiesagainst Factor VIII.

In yet another embodiment, combination therapy comprising administrationof Factor VIII and a FVIII bypass agent is provided to an individualbased on the predicted risk of developing antibodies against FactorVIII. In one specific embodiment, a combination therapy is provided toan individual with a predicted decreased risk of developing antibodiesagainst Factor VIII. In another specific embodiment, a combinationtherapy is provided to an individual with a predicted increased risk ofdeveloping antibodies against Factor VIII.

In one embodiment, the method further comprises adjusting a dosage of atreatment comprising administration of Factor VIII to the individualbased on the predicted risk of developing antibodies against FactorVIII. In a specific embodiment, a dosage of Factor VIII to beadministered to an individual with a predicted decreased risk ofdeveloping antibodies against Factor VIII is increased. In anotherspecific embodiment, a dosage of Factor VIII to be administered to anindividual with a predicted increased risk of developing antibodiesagainst Factor VIII is decreased.

In another embodiment, the method further comprises adjusting the dosageand/or frequency of Factor VIII administration in a combination therapybased on the predicted risk of developing antibodies against FVIII. Inone embodiment, the method comprises increasing the dosage or frequencyof Factor VIII administered in a combination therapy to an individualwith a predicted decreased risk of developing antibodies against FactorVIII. In another embodiment, the method comprises decreasing the dosageor frequency of Factor VIII administered in a combination therapy to anindividual with a predicted increased risk of developing antibodiesagainst Factor VIII.

In another embodiment, the method further comprises adjusting the dosageand/or frequency of a non-FVIII hemostatic agent administered in acombination therapy based on the predicted risk of developing antibodiesagainst FVIII. In one embodiment, the method comprises increasing thedosage or frequency of a non-FVIII hemostatic agent administered in acombination therapy to an individual with a predicted increased risk ofdeveloping antibodies against Factor VIII. In another embodiment, themethod comprises decreasing the dosage or frequency of a non-FVIIIhemostatic agent administered in a combination therapy to an individualwith a predicted decreased risk of developing antibodies against FactorVIII.

In another embodiment, the method further comprises adjusting the dosageand/or frequency of both Factor VIII and a non-FVIII hemostatic agentadministered in a combination therapy based on the predicted risk ofdeveloping antibodies against FVIII. In this fashion, a combinationtherapy may be optimized for an individual with a specific predictedrisk of developing antibodies against FVIII. Optimization of the dosageand/or frequency of Factor VIII and non-FVIII hemostatic agents incombination therapy may be achieved by any combination of increasing thefrequency of FVIII administration, decreasing the frequency of FVIIIadministration, increasing the dosage of FVIII, decreasing the dosage ofFVIII, increasing the frequency of non-FVIII hemostatic agentadministration, decreasing the frequency of non-FVIII hemostatic agentadministration, increasing the dosage of a non-FVIII hemostatic agent,and decreasing the dosage of a non-FVIII hemostatic agent.

In a specific embodiment, the method comprises increasing the frequencyand/or dosage of FVIII and decreasing the frequency and/or dosage of anon-FVIII hemostatic agent administered to an individual with apredicted decreased risk of developing antibodies against Factor VIII.

In another specific embodiment, the method comprises decreasing thefrequency and/or dosage of FVIII and increasing the frequency and/ordosage of a non-FVIII hemostatic agent administered to an individualwith a predicted increased risk of developing antibodies against FactorVIII.

In a preferred embodiment, the method comprises the detection of atleast one SNP selected from those listed in Table 4. In a specificembodiment, the method comprises the detection of at least on SNPselected from the group consisting of rs12368829, rs4147385, rs11744216,rs1863993, rs17535213, rs10072056, rs10054825, rs12546235, rs4242389,rs2071336, rs414634, rs17725712, rs11773821, rs8005905, and rs9482888.In one embodiment, at least one detected SNP is rs12368829. In anotherembodiment, at least one detected SNP is rs4147385. In anotherembodiment, at least one detected SNP is rs11744216. In anotherembodiment, at least one detected SNP is rs1863993. In anotherembodiment, at least one detected SNP is rs17535213. In anotherembodiment, at least one detected SNP is rs10072056.

In another embodiment, at least one detected SNP is rs10054825. Inanother embodiment, at least one detected SNP is rs12546235. In anotherembodiment, at least one detected SNP is rs4242389. In anotherembodiment, at least one detected SNP is rs2071336. In anotherembodiment, at least one detected SNP is rs414634. In anotherembodiment, at least one detected SNP is rs17725712. In anotherembodiment, at least one detected SNP is rs11773821.

In another embodiment, at least one detected SNP is rs8005905. Inanother embodiment, at least one detected SNP is rs9482888.

B. Predictive Markers

Among other aspects, the present invention provides novel markersconsisting of SNPs for predicting the risk of developing antibodiesagainst Factor VIII (FVIII) in an individual diagnosed with HemophiliaA. Any individual SNP provided in Tables 1 to 4 may be used inconjunction with any other individual SNP provided in Tables 1 to 4 inthe methods provided herein for the risk of developing antibodiesagainst Factor VIII (FVIII) in an individual diagnosed with HemophiliaA.

As such, the present invention contemplates methods for detecting theidentity of the nucleotide corresponding to the genomic position of anysingle SNP listed in Tables 1 to 4 in a biological sample from anindividual diagnosed with Hemophilia A. In another embodiment, themethod comprises detecting the identity of the nucleotide correspondingto the genomic position of at least 2 SNPs listed in Tables 1 to 4 in asample from an individual diagnosed with Hemophilia A. In yet otherembodiments, methods are provided for detecting the identity of thenucleotide corresponding to the genomic position of at least 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43,44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61,62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79,80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97,98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112,113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126,127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140,141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154,155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168,169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182,183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196,197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210,211, 212, 213, 214, 215, 216, 217, 218, 219, 220, more, or all of theSNPs listed in Tables 1 to 4.

In a related embodiment, the present invention contemplates methods fordetecting the presence of any SNP listed in Tables 1 to 4 in abiological sample from an individual diagnosed with Hemophilia A. Inanother embodiment, the method comprises detecting the presence of atleast 2 SNPs listed in Tables 1 to 4 in a sample from an individualdiagnosed with Hemophilia A. In yet other embodiments, methods areprovided for detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46,47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64,65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82,83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100,101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114,115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128,129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142,143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156,157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170,171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184,185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198,199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212,213, 214, 215, 216, 217, 218, 219, 220, more, or all of the SNPs listedin Tables 1 to 4. Generally, detecting the presence of at least one SNPin a biological sample from an individual diagnosed with Hemophilia Amay comprise detecting the identity of the nucleotide corresponding tothe genomic position of multiple SNPs listed in Tables 1 to 4.

In certain embodiments, these SNPs may be used in conjunction with othermarkers known in the art as useful to help predict the risk ofdeveloping antibodies against Factor VIII (FVIII) in an individualdiagnosed with Hemophilia A. Non-limiting examples of other markersinclude, various epitopes and allelic variations of the Factor VIII geneand gene product (see, Millar DS et al., Hum Genet. 1990 December;86(2):219-27; Kazazian HH Jr et al., Nature 1988 Mar. 10;332(6160):164-6; and Ostertag EM et al., Annu Rev Genet. 2001;35:501-38, the disclosures of which are hereby incorporated by referencein their entireties for all purposes).

Genomic information regarding the SNPs listed in Tables 1 to 4 can beobtained from the ENTREZ SNP database accessible via the website for theNational Center for Biotechnology Information (NCBI). For example, ascan be found on the server mentioned above, SNP rs12368829 correspondsto an A/G single nucleotide polymorphism (SNP) at position 94,473,201 ofhuman chromosome 12 according to build 37.1 of the Celera whole genomesequence. The sequence flanking the SNP comprises the followingsequence, with the SNP position underlined in brackets:

(SEQ ID NO: 1) TTGCCACTACTTGTCTCCAAAGAAAC[A/G]TAAGAATGCTTTATCATACAACAGT,Based on the sequence information provided by the NCBI server, one ofskill in the art will readily be able to determine the identity of thenucleotide at a position corresponding to any one of the SNPs listed inTables 1 to 4 in a biological sample from an individual diagnosed withHemophilia A. Accordingly, Applicants hereby incorporate the informationprovided on the NCBI server for each of the SNPs listed in Tables 1 to 4into the present application in its entirety for all purposes.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1003854. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1003854 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1003854 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs10054825. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs10054825 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs10054825 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs10072056. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs10072056 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs10072056 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1007212. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1007212 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1007212 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs10074391. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs10074391 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs10074391 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1007822. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1007822 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1007822 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs10104302. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs10104302 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs10104302 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs10165797. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs10165797 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs10165797 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs10261447. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs10261447 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs10261447 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs10406354. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs10406354 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs10406354 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1041067. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1041067 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1041067 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1044141. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1044141 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1044141 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1046780. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1046780 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1046780 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs10497208. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs10497208 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs10497208 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1050382. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1050382 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1050382 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs10514071. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs10514071 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs10514071 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1058240. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1058240 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1058240 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1062069. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1062069 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1062069 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1075846. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1075846 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1075846 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs10772120. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs10772120 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs10772120 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs10789841. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs10789841 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs10789841 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs10797666. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs10797666 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs10797666 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs10807350. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs10807350 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs10807350 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs10836342. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs10836342 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs10836342 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs10854166. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs10854166 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs10854166 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs10972149. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs10972149 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs10972149 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs10977434. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs10977434 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs10977434 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs11015985. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs11015985 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs11015985 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs11032349. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs11032349 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs11032349 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1105238. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1105238 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1105238 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs11168267. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs11168267 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs11168267 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs11214108. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs11214108 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs11214108 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs11237451. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs11237451 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs11237451 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs11265416. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs11265416 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs11265416 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1131510. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1131510 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1131510 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs11574113. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs11574113 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs11574113 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs11740298. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs11740298 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs11740298 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs11744216. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs11744216 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs11744216 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs11773821. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs11773821 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs11773821 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs11780679. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs11780679 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs11780679 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs11833550. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs11833550 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs11833550 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs11852361. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs11852361 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs11852361 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs11952962. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs11952962 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs11952962 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12001295. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12001295 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12001295 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12034383. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12034383 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12034383 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12039194. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12039194 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12039194 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12051769. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12051769 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12051769 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1206486. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1206486 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1206486 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12185980. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12185980 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12185980 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12310405. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12310405 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12310405 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12325842. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12325842 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12325842 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12368829. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12368829 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12368829 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12451415. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12451415 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12451415 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12506181. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12506181 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12506181 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12546235. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12546235 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12546235 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12546235. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12546235 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12546235 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12625871. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12625871 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12625871 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1264456. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1264456 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1264456 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12667537. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12667537 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12667537 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1267843. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1267843 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1267843 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12692566. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12692566 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12692566 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12810163. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12810163 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12810163 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12814009. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12814009 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12814009 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12831813. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12831813 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12831813 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12881815. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12881815 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12881815 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12959952. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12959952 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12959952 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs12969613. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs12969613 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs12969613 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs13042473. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs13042473 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs13042473 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs13096099. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs13096099 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs13096099 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs13172280. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs13172280 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs13172280 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs13173943. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs13173943 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs13173943 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs13206518. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs13206518 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs13206518 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1378796. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1378796 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1378796 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1411479. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1411479 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1411479 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1436522. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1436522 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1436522 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1457238. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1457238 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1457238 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1465073. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1465073 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1465073 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1519602. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1519602 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1519602 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1523474. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1523474 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1523474 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1552323. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1552323 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1552323 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1567748. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1567748 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1567748 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1573706. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1573706 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1573706 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs161021. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs161021in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs161021 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs161042. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs161042in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs161042 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1638006. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1638006 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1638006 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs169142. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs169142in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs169142 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs17110948. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs17110948 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs17110948 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs17113227. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs17113227 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs17113227 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs17141840. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs17141840 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs17141840 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs17201075. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs17201075 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs17201075 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs17228097. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs17228097 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs17228097 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1724120. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1724120 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1724120 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs17283264. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs17283264 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs17283264 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs17317153. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs17317153 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs17317153 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs17419586. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs17419586 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs17419586 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs17535213. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs17535213 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs17535213 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs17652304. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs17652304 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs17652304 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs17671456. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs17671456 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs17671456 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs17725712. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs17725712 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs17725712 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs17748322. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs17748322 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs17748322 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs17763453. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs17763453 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs17763453 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs17811425. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs17811425 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs17811425 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs17815972. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs17815972 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs17815972 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16; 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1781795. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1781795 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1781795 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs17834679. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs17834679 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs17834679 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor. VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs17875513. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs17875513 in a biological sample from the individual; and predictingthe risk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs17875513 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1797646. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1797646 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1797646 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1797647. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1797647 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1797647 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1838065. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1838065 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1838065 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1863993. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1863993 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1863993 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1865462. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1865462 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1865462 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1877563. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1877563 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1877563 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1882019. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1882019 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1882019 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1884564. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1884564 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1884564 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1885831. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1885831 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1885831 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1892803. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1892803 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1892803 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1918309. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1918309 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1918309 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1983165. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1983165 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1983165 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs1984399. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs1984399 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs1984399 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2010452. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2010452 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2010452 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2020902. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2020902 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2020902 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2069933. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2069933 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2069933 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2070123. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2070123 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2070123 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2070783. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2070783 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2070783 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2071081. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2071081 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2071081 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2071336. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2071336 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2071336 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2076620. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2076620 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2076620 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2076846. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2076846 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2076846 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs208250. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs208250in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs208250 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs210431. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs210431in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs210431 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2157605. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2157605 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2157605 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2163057. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2163057 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2163057 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2179694. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2179694 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2179694 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2227562. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2227562 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2227562 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2227827. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2227827 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2227827 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2231375. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2231375 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2231375 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2238337. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2238337 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2238337 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2242660. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2242660 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2242660 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2255364. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2255364 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2255364 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2267908. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2267908 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2267908 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2268890. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2268890 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2268890 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2275603. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2275603 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2275603 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2278324. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2278324 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2278324 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2279590. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2279590 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2279590 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2283539. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2283539 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2283539 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2286414. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2286414 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2286414 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2287768. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2287768 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2287768 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2288522. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2288522 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2288522 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2295616. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2295616 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2295616 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2296449. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2296449 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2296449 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18; 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2298877. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2298877 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2298877 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2302267. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2302267 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2302267 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2302759. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2302759 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2302759 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2302821. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2302821 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2302821 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2305340. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2305340 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2305340 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2335478. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2335478 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2335478 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs241430. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs241430in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs241430 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs244076. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs244076in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs244076 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs244090. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs244090in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs244090 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs244091. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs244091in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs244091 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs244656. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs244656in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs244656 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs246390. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs246390in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs246390 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs246392. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs246392in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs246392 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs246394. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs246394in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs246394 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs246395. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs246395in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs246395 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2569190. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2569190 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2569190 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2575674. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2575674 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2575674 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2584019. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2584019 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2584019 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2595204. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2595204 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2595204 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2596606. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2596606 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2596606 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2838733. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2838733 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2838733 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2844463. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2844463 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2844463 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2853884. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2853884 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2853884 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2869460. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2869460 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2869460 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2869461. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2869461 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2869461 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs2879097. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs2879097 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs2879097 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs3024486. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs3024486 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs3024486 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs3024498. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs3024498 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs3024498 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs304839. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs304839in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs304839 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs310247. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs310247in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs310247 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs31519. In oneembodiment, a method is provided for predicting the risk of developingantibodies against FVIII in an individual diagnosed with Hemophilia Acomprising the steps of detecting the presence SNP rs31519 in abiological sample from the individual; and predicting the risk of theindividual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs31519 is predictive of an increased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs3181096. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs3181096 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs3181096 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs3211821. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs3211821 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs3211821 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs3211834. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs3211834 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs3211834 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs3733236. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs3733236 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs3733236 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs3733678. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs3733678 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs3733678 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs3736101. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs3736101 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs3736101 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs3736395. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs3736395 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs3736395 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs3788151. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs3788151 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs3788151 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs3795326. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs3795326 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs3795326 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs3797390. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs3797390 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs3797390 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs3815003. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs3815003 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs3815003 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs3816724. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs3816724 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs3816724 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs3819496. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs3819496 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs3819496 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs3826392. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs3826392 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs3826392 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs3828016. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs3828016 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs3828016 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs3845422. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs3845422 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs3845422 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs390406. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs390406in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs390406 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4027402. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4027402 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4027402 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4077341. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4077341 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4077341 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4094864. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4094864 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4094864 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4104. In oneembodiment, a method is provided for predicting the risk of developingantibodies against FVIII in an individual diagnosed with Hemophilia Acomprising the steps of detecting the presence SNP rs4104 in abiological sample from the individual; and predicting the risk of theindividual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs4104 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs414634. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs414634in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs414634 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4147385. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4147385 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4147385 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2; 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs424051. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs424051in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs424051 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4242389. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4242389 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4242389 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4245886. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4245886 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4245886 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4251520. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4251520 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4251520 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4253655. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4253655 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4253655 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs440238. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs440238in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs440238 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4462251. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4462251 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4462251 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4472605. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4472605 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4472605 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4485556. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4485556 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4485556 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4498385. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4498385 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4498385 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4572808. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4572808 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4572808 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4639174. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4639174 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4639174 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4646077. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4646077 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4646077 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4698806. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4698806 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4698806 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4724231. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4724231 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4724231 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4752894. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4752894 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4752894 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4752896. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4752896 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4752896 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4752904. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4752904 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4752904 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4756331. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4756331 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4756331 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4798598. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4798598 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4798598 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4820059. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4820059 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4820059 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4902264. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4902264 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4902264 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4953292. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4953292 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4953292 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4955104. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4955104 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4955104 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4955272. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4955272 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4955272 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs4966019. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs4966019 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs4966019 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs496888. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs496888in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs496888 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs499205. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs499205in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs499205 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs509749. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs509749in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs509749 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs5743220. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs5743220 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs5743220 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs5743740. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs5743740 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs5743740 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs5746154. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs5746154 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs5746154 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs599563. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs599563in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs599563 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs5996577. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs5996577 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs5996577 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6016685. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6016685 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6016685 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6021183. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6021183 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6021183 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6058391. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6058391 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6058391 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6060855. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6060855 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6060855 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6065460. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6065460 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6065460 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6065467. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6065467 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6065467 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6093584. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6093584 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6093584 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs613613. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs613613in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs613613 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6214. In oneembodiment, a method is provided for predicting the risk of developingantibodies against FVIII in an individual diagnosed with Hemophilia Acomprising the steps of detecting the presence SNP rs6214 in abiological sample from the individual; and predicting the risk of theindividual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs6214 is predictive of an increased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs638251. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs638251in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs638251 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6476985. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6476985 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6476985 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6482644. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6482644 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6482644 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6482647. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6482647 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6482647 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6544865. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6544865 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6544865 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6580942. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6580942 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6580942 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs660597. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs660597in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs660597 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6621980. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6621980 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6621980 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6670616. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6670616 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6670616 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6742576. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6742576 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6742576 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6751395. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6751395 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6751395 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6769530. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6769530 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6769530 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6780432. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6780432 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6780432 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6782288. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6782288 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6782288 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6829390. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6829390 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6829390 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6837303. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6837303 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6837303 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6850557. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6850557 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6850557 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6863088. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6863088 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6863088 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs6917187. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs6917187 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs6917187 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs704697. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs704697in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs704697 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs704853. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs704853in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs704853 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs706121. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs706121in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs706121 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs7072398. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs7072398 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs7072398 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs7099752. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs7099752 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs7099752 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs7124275. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs7124275 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs7124275 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs7130876. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs7130876 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs7130876 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs7170919. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs7170919 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs7170919 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs717176. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs717176in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs717176 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs7246376. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs7246376 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs7246376 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs728373. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs728373in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs728373 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs7289754. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs7289754 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs7289754 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs7290696. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs7290696 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs7290696 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs731305. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs731305in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs731305 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs7348444. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs7348444 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs7348444 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs7359387. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs7359387 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs7359387 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs7541717. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs7541717 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs7541717 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs7559522. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs7559522 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs7559522 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs763361. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs763361in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs763361 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs7641625. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs7641625 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs7641625 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs7647903. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs7647903 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs7647903 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs766502. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs766502in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs766502 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs7690305. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs7690305 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs7690305 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs7692976. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs7692976 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs7692976 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP 146106438. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP146106438 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP 146106438 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs7732671. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs7732671 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs7732671 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs7851161. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs7851161 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs7851161 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs791587. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs791587in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs791587 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs793816. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs793816in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs793816 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs7987909. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs7987909 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs7987909 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs8005905. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs8005905 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs8005905 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs805274. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs805274in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs805274 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs805287. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs805287in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs805287 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs8064821. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs8064821 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs8064821 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs8078439. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs8078439 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs8078439 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs8086815. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs8086815 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs8086815 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs831603. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs831603in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs831603 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs832517. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs832517in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs832517 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs866484. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs866484in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs866484 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs872071. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs872071in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs872071 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs875258. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs875258in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs875258 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs878081. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs878081in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs878081 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs896769. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs896769in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs896769 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs910682. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs910682in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs910682 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs926479. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs926479in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs926479 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs927010. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs927010in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs927010 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs927335. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs927335in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs927335 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs9310940. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs9310940 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs9310940 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs9313487. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs9313487 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs9313487 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs933226. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs933226in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs933226 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs9426315. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs9426315 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs9426315 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs9482888. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs9482888 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs9482888 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs9487735. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs9487735 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs9487735 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs949664. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs949664in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs949664 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs970283. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs970283in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs970283 is predictive of a decreased risk of developingantibodies against Factor VIII. In one embodiment, the method furthercomprises assigning a therapy comprising administration of Factor VIIIto the individual. In another embodiment, the method further comprisesassigning a therapy comprising Factor VIII bypass therapy to theindividual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs976881. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNP rs976881in a biological sample from the individual; and predicting the risk ofthe individual of developing antibodies to FVIII. In one embodiment, thepresence of SNP rs976881 is predictive of an increased risk ofdeveloping antibodies against Factor VIII. In one embodiment, the methodfurther comprises assigning a therapy comprising administration ofFactor VIII to the individual. In another embodiment, the method furthercomprises assigning a therapy comprising Factor VIII bypass therapy tothe individual. In another embodiment, the method further comprisesincreasing a dosage of a therapy comprising administration of FVIII tobe administered to the individual. In another embodiment, the methodfurther comprises decreasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises detecting the presence of atleast a second SNP selected from the group consisting of the SNPs listedin Tables 1, 2, 3, and 4. In another embodiment, the method furthercomprises detecting the presence of at least 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100,125, 150, 175, 200, or more SNPs selected from the group consisting ofthe SNPs listed in Tables 1, 2, 3, and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs9817149. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs9817149 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs9817149 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs9826296. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs9826296 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs9826296 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs9831803. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs9831803 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs9831803 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs9862163. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs9862163 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs9862163 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs9867325. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs9867325 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs9867325 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs9892152. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs9892152 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs9892152 is predictive of an increasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

In one embodiment, the present invention provides a marker useful forpredicting the risk of developing antibodies against FVIII in anindividual diagnosed with Hemophilia A consisting of SNP rs9991904. Inone embodiment, a method is provided for predicting the risk ofdeveloping antibodies against FVIII in an individual diagnosed withHemophilia A comprising the steps of detecting the presence SNPrs9991904 in a biological sample from the individual; and predicting therisk of the individual of developing antibodies to FVIII. In oneembodiment, the presence of SNP rs9991904 is predictive of a decreasedrisk of developing antibodies against Factor VIII. In one embodiment,the method further comprises assigning a therapy comprisingadministration of Factor VIII to the individual. In another embodiment,the method further comprises assigning a therapy comprising Factor VIIIbypass therapy to the individual. In another embodiment, the methodfurther comprises increasing a dosage of a therapy comprisingadministration of FVIII to be administered to the individual. In anotherembodiment, the method further comprises decreasing a dosage of atherapy comprising administration of FVIII to be administered to theindividual. In another embodiment, the method further comprisesdetecting the presence of at least a second SNP selected from the groupconsisting of the SNPs listed in Tables 1, 2, 3, and 4. In anotherembodiment, the method further comprises detecting the presence of atleast 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or more SNPsselected from the group consisting of the SNPs listed in Tables 1, 2, 3,and 4.

C. Methods for Detecting SNPs

The present invention relies on routine techniques in the field ofrecombinant genetics. Basic texts disclosing the general methods of usein this invention include Sambrook et al., Molecular Cloning, ALaboratory Manual (3rd ed. 2001); Kriegler, Gene Transfer andExpression: A Laboratory Manual (1990); and Current Protocols inMolecular Biology (Ausubel et al., eds., 1994)). Oligonucleotides thatare not commercially available can be chemically synthesized accordingto the solid phase phosphoramidite triester method first described byBeaucage & Caruthers, Tetrahedron Letts. 22:1859-1862 (1981), using anautomated synthesizer, as described in Van Devanter et. al., NucleicAcids Res. 12:6159-6168 (1984). Purification of oligonucleotides is byeither native acrylamide gel electrophoresis or by anion-exchange HPLCas described in Pearson & Reanier, J. Chrom. 255:137-149 (1983).

Any suitable method can be used to detect (i.e. screen for or identify)a SNP, e.g., restriction fragment length polymorphisms andelectrophoretic gel analysis or mass spectroscopy, or PCR analysis.Various real-time PCR methods can be used to detect SNPs, including,e.g., Taqman or molecular beacon-based assays (e.g., U.S. Pat. Nos.5,210,015; 5,487,972; Tyagi et al., Nature Biotechnology 14:303 (1996);and PCT WO 95/13399) are useful to monitor for the presence of absenceof a SNP. Additional SNP detection methods include, e.g., DNAsequencing, sequencing by hybridization, dot blotting, oligonucleotidearray (DNA chip or bead chip) hybridization analysis, or are describedin, e.g., U.S. Pat. No. 6,177,249; Landegren et al., Genome Research,8:769-776 (1998); Botstein et al., Am J Human Genetics 32:314-331(1980); Meyers et al., Methods in Enzymology 155:501-527 (1987); Keen etal., Trends in Genetics 7:5 (1991); Myers et al., Science 230:1242-1246(1985); and Kwok et al., Genomics 23:138-144 (1994).

Analysis of the genotype of an nucleic acid marker can be performedusing techniques known in the art including, without limitation,microarrays, polymerase chain reaction (PCR)-based analysis, sequenceanalysis, and electrophoretic analysis. A non-limiting example of aPCR-based analysis includes a Taqman® allelic discrimination assayavailable from Applied Biosystems. Non-limiting examples of sequenceanalysis include Maxam-Gilbert sequencing, Sanger sequencing, capillaryarray DNA sequencing, thermal cycle sequencing (Sears et al.,Biotechniques, 13:626-633 (1992)), solid-phase sequencing (Zimmerman etal., Methods Mol. Cell Biol., 3:39-42 (1992)), sequencing with massspectrometry such as matrix-assisted laser desorption/ionizationtime-of-flight mass spectrometry (MALDI-TOF/MS; Fu et al., NatureBiotech., 16:381-384 (1998)), and sequencing by hybridization (Chee etal., Science, 274:610-614 (1996); Drmanac et al., Science, 260:1649-1652(1993); Drmanac et al., Nature Biotech., 16:54-58 (1998)). Non-limitingexamples of electrophoretic analysis include slab gel electrophoresissuch as agarose or polyacrylamide gel electrophoresis, capillaryelectrophoresis, and denaturing gradient gel electrophoresis. Othermethods for genotyping a subject at a polymorphic site include, e.g.,the INVADER® assay from Third Wave Technologies, Inc., restrictionfragment length polymorphism (RFLP) analysis, allele-specificoligonucleotide hybridization, a heteroduplex mobility assay, singlestrand conformational polymorphism (SSCP) analysis, single-nucleotideprimer extension (SNUPE) and pyrosequencing.

A detectable moiety can be used in the assays described herein. A widevariety of detectable moieties can be used, with the choice of labeldepending on the sensitivity required, ease of conjugation with theantibody, stability requirements, and available instrumentation anddisposal provisions. Suitable detectable moieties include, but are notlimited to, radionuclides, fluorescent dyes (e.g., fluorescein,fluorescein isothiocyanate (FITC), Oregon Green™, rhodamine, Texas red,tetrarhodimine isothiocynate (TRITC), Cy3, Cy5, etc.), fluorescentmarkers (e.g., green fluorescent protein (GFP), phycoerythrin, etc.),autoquenched fluorescent compounds that are activated bytumor-associated proteases, enzymes (e.g., luciferase, horseradishperoxidase, alkaline phosphatase, etc.), nanoparticles, biotin,digoxigenin, and the like.

Probes are typically labeled either directly, as with isotopes,chromophores, lumiphores, chromogens, or indirectly, such as withbiotin, to which a streptavidin complex may later bind. Thus, thedetectable labels used in the assays of the present invention can beprimary labels (where the label comprises an element that is detecteddirectly or that produces a directly detectable element) or secondarylabels (where the detected label binds to a primary label, e.g., as iscommon in immunological labeling). Typically, labeled signal nucleicacids are used to detect hybridization. Complementary nucleic acids orsignal nucleic acids may be labeled by any one of several methodstypically used to detect the presence of hybridized polynucleotides. Themost common method of detection is the use of autoradiography with ³H,¹²⁵I, ³⁵S, ¹⁴C, or ³²P-labeled probes or the like.

Other labels include, e.g., ligands that bind to labeled antibodies,fluorophores, chemiluminescent agents, enzymes, and antibodies which canserve as specific binding pair members for a labeled ligand. Anintroduction to labels, labeling procedures and detection of labels isfound in Polak and Van Noorden Introduction to Immunocytochemistry, 2nded., Springer Verlag, NY (1997); and in Haugland Handbook of FluorescentProbes and Research Chemicals, a combined handbook and cataloguePublished by Molecular Probes, Inc. (1996).

In general, a detector which monitors a particular probe or probecombination is used to detect the detection reagent label. Typicaldetectors include spectrophotometers, phototubes and photodiodes,microscopes, scintillation counters, cameras, film and the like, as wellas combinations thereof. Examples of suitable detectors are widelyavailable from a variety of commercial sources known to persons of skillin the art. Commonly, an optical image of a substrate comprising boundlabeling moieties is digitized for subsequent computer analysis.

A variety of automated solid-phase assay techniques are alsoappropriate. For instance, very large scale immobilized polymer arrays(VLSIPS™), available from Affymetrix, Inc. (Santa Clara, Calif.) can beused to detect changes in expression levels of a plurality of genesinvolved in the same regulatory pathways simultaneously. See, Tijssen,supra., Fodor et al. (1991) Science, 251: 767-777; Sheldon et al. (1993)Clinical Chemistry 39(4): 718-719, and Kozal et al. (1996) NatureMedicine 2(7): 753-759.

The nucleic acids used in this invention can be either positive ornegative probes. Positive probes bind to their targets and the presenceof duplex formation is evidence of the presence of the target. Negativeprobes fail to bind to the suspect target and the absence of duplexformation is evidence of the presence of the target. For example, theuse of a wild type specific nucleic acid probe or PCR primers may serveas a negative probe in an assay sample where only the nucleotidesequence of interest is present.

The sensitivity of the hybridization assays may be enhanced through useof a nucleic acid amplification system that multiplies the targetnucleic acid being detected. Examples of such systems include thepolymerase chain reaction (PCR) system, in particular RT-PCR or realtime PCR, and the ligase chain reaction (LCR) system. Other methodsrecently described in the art are the nucleic acid sequence basedamplification (NASBA, Cangene, Mississauga, Ontario) and Q BetaReplicase systems. These systems can be used to directly identifymutants where the PCR or LCR primers are designed to be extended orligated only when a selected sequence is present. Alternatively, theselected sequences can be generally amplified using, for example,nonspecific PCR primers and the amplified target region later probed fora specific sequence indicative of a mutation.

In some embodiments of the present invention, the target nucleic acid orthe probe is immobilized on a solid support. Solid supports suitable foruse in the assays of the invention are known to those of skill in theart. As used herein, a solid support is a matrix of material in asubstantially fixed arrangement. One preferred example is the Illumina®BeadChip array. The array comprises silica beads which areself-assembled into ordered microwells. Each 3 gm silica bead comprisesa plurality of 50mer, transcript-specific oligonucleotide probes thathave been immobilized on the bead. To generate a BeadChip, thousands totens of thousands of unique oligonucleotides, each complementary to adifferent target sequence, are synthesized. These oligos are thenimmobilized in separate reactions to the beads, generating acorresponding number of unique bead types. The beads are pooledtogether, and then loaded by a self-assembly process into microwellsthat have been etched into the surface of a BeadChip. Each bead type isrepresented on the array surface an average of more than thirty times.

In some embodiments, the identification of a single nucleotidepolymorphism of the present invention is accomplished through the use ofa whole-genome amplification method. One preferred example is theIllumina® Infinium® assay. Briefly, 750 ng of human genomic DNA isisothermally amplified overnight. The amplified product is thenfragmented by a controlled enzymatic digestion. The DNA is thenprecipitated and resuspended and applied to a BeadChip that has beenprepared for hybridization. DNA samples are applied to the BeadChip andincubated overnight. The amplified and fragmented DNA samples anneal tolocus-specific 50-mers (on beads). Each bead type corresponds to eachallele per SNP locus. After hybridization, allelic specificity isconferred by enzymatic base extension and revealed by fluorescentstaining.

IV. Compositions, Kits, and Arrays

The invention also provides compositions, kits, and arrays forpracticing the methods described herein using polynucleotides of theinvention.

In some embodiments, the oligonucleotides, kits, and arrays of thepresent invention may be used to predict the risk of an individualdeveloping antibodies to factor VIII (FVIII) and to adjust a dosage ofFVIII therapy received by the individual. In some embodiments, theoligonucleotides, kits, and arrays of the present invention may be usedto predict the risk of an individual developing antibodies to FVIII andto adjust a dosage of bypass therapy received by the individual.

A. Probes

In exemplary embodiments, a kit described herein comprises a captureprobe or capture probe set. Capture probes sets comprise a plurality of“capture probes,” which are compounds used to detect the presence orabsence of, or to quantify, relatively or absolutely, a target speciesor target sequence. Generally, a capture probe allows the attachment ofa target sequence to a solid support for the purposes of detection asfurther described herein. Attachment of the target species to thecapture binding ligand can be direct or indirect and can be covalent ornoncovalent. Capture probes that bind directly to a target species maybe said to be “selective” for, “specifically bind” or “selectively bind”their target. It should be noted that capture probes are designed to beperfectly or substantially complementary to either of the strands (e.g.either the sense or the antisense strand) of a double strandedpolynucleotide, such as a gene. Thus, in some cases, a capture probedescribed herein is perfectly or substantially complementary to thesense strand; that is, assuming the sense strand is referred to as“Watson”, the capture probe would be “Crick”. In some cases, a captureprobe described herein is perfectly or substantially complementary tothe antisense strand. For detecting a SNP, a capture probe selective foran allele of a gene typically spans the one or more nucleic acids thatdiffers from corresponding nucleic acids in a different allele of agene. For detecting an insertion, a capture probe selective for anallele of a gene typically spans one or more nucleic acids that arepresent compared to the corresponding site in a different allele of agene in which the nucleic acids are absent. For detecting a deletion, acapture probe selective for an allele of a gene typically spans a sitewhere one or more nucleic acids are absent compared to the correspondingsite in a different allele of a gene in which the nucleic acids arepresent.

Capture probes that “selectively bind” to or are “selective” for (i.e.,are “complementary” or “substantially complementary” to) a targetnucleic acid find use in the present invention. “Complementary” or“substantially complementary” refers to the hybridization or basepairing or the formation of a duplex between nucleotides or nucleicacids, such as, for instance, between the two strands of a doublestranded DNA molecule or between an oligonucleotide primer and a primerbinding site on a single stranded nucleic acid. Complementarynucleotides are, generally, A and T (or A and U), or C and G. Two singlestranded RNA or DNA molecules may be said to be substantiallycomplementary when the nucleotides of one strand, optimally aligned andcompared and with appropriate nucleotide insertions or deletions, pairwith at least about 80% of the nucleotides of the other strand, usuallyat least about 90% to 95%, and more preferably from about 98% to 100%,and in some embodiments, at least a percentage selected from 90%, 91%,92%, 93%, 94%, 95%, 96%, 97%, 98% and 99%. Where one single stranded RNAor DNA molecule is shorter than another, the two single stranded RNA orDNA molecules may be said to be substantially complementary when thenucleotides of the longer strand, optimally aligned and compared andwith appropriate nucleotide insertions or deletions, pair with at leastabout 80% of the nucleotides of the shorter strand, usually at leastabout 90% to 95%, and more preferably from about 98% to 100%, and insome embodiments, at least a percentage selected from 90%, 91%, 92%,93%, 94%, 95%, 96%, 97%, 98% and 99%. Alternatively, substantialcomplementarity exists (i.e., one sequence is selective for another)when an RNA or DNA strand will hybridize under selective hybridizationconditions (for example, stringent conditions or high stringencyconditions as known in the art) to its complement. Typically, selectivehybridization will occur when there is at least about 65%complementarity over a stretch of at least 14 to 25 nucleotides,preferably at least about 75%, more preferably at least about 90% (or91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%) complementarity. (See, M.Kanehisa, Nucleic Acids Res., 2004, 12: 203.) In some embodiments, theterm “bind” refers to binding under high stringency conditions. In someembodiments, a capture probe that selectively binds to or is selectivefor a target is perfectly complementary to the target. In someembodiments, a capture probe that selectively binds to or is selectivefor a target is substantially complementary to the target.

“Duplex” means at least two oligonucleotides and/or polynucleotides thatare fully or partially complementary undergo Watson-Crick type basepairing among all or most of their nucleotides so that a stable complexis formed. The terms “annealing” and “hybridization” are usedinterchangeably to mean the formation of a stable duplex. In oneembodiment, stable duplex means that a duplex structure is not destroyedby a stringent wash, e.g., conditions including temperature of about 5°C. less than the T_(m) of a strand of the duplex and low monovalent saltconcentration, e.g. less than 0.2 M, or less than 0.1 M. “Perfectlymatched” in reference to a duplex means that the poly- oroligonucleotide strands making up the duplex form a double strandedstructure with one another such that every nucleotide in each strandundergoes Watson-Crick basepairing with a nucleotide in the otherstrand. The term “duplex” includes the pairing of nucleoside analogs,such as deoxyinosine, nucleosides with 2-aminopurine bases, PNAs, andthe like, that may be employed. A “mismatch” in a duplex between twooligonucleotides or polynucleotides means that a pair of nucleotides inthe duplex fails to undergo Watson-Crick bonding.

In exemplary embodiments, each of the probes of a capture probe set issuitable for distinguishing at least two different alleles of a givengene (e.g., a SNP associated with a risk risk of developing antibodiesagainst Factor VIII (FVIII) in an individual diagnosed with Hemophilia

A). The probes or capture probe sets described herein can be used todetermine a polymorphism at a gene locus. As understood in the art, an“allele” refers to a particular alternative form of a gene. Forconvenience, the term “allele” as used herein can also refer to acombination of alleles at multiple loci that are transmitted together onthe same chromosome. That is, an allele can refer to a haplotype. Anallele can be characterized, for example, by substitution, insertion ordeletion of one or more bases relative to a different allele. A captureprobe could thus, in various examples, span a polymorphic site of thegene, span one or more insertions or span nucleic acids flanking adeletion.

An allele may be referred to in various ways. For example, an allele maybe referred to by a substitution of a nucleotide for another in a parentpolynucleotide strand (e.g., genomic DNA, mRNA, fragments thereof,amplification products thereof and other polynucleotides disclosedherein) or by the substitution of an amino acid for another in a parentpolypeptide strand (e.g., a polypeptide resulting from translation of apolynucleotide). In some instances, a reference to an amino acidsubstitution corresponds to a nucleotide variation in the gene thatcauses that amino acid substitution in the polypeptide resulting fromexpression of the gene as understood in the art. Where reference is madeto a substitution, both a parent molecule (e.g., gene) and a moleculecontaining the substitution relative to the parent are contemplated andeither or both alleles may be probed. Where reference is made to aninsertion, both a parent molecule (e.g., gene) and a molecule containingthe insertion relative to the parent is contemplated and either or bothalleles may be probed. Where reference is made to a deletion, both aparent molecule (e.g., gene) and a molecule containing the deletionrelative to the parent is contemplated and either or both alleles may beprobed.

In one embodiment, a capture probe set comprises a probe that isselective for an allele of a gene, (e.g., a gene associated with a SNPlisted in any one of Tables 1 to 4). In one embodiment, a capture probeset comprises a pair of probes, one of which is selective for a firstallele of a gene and one of which is selective for a second allele ofthe gene. In some embodiments, a capture probe set comprises a pair ofprobes, one of which is selective for a wildtype allele of the gene andone of which is selective for a mutant (or “variant”) allele of thegene. The term “wildtype” can in some embodiments refer to a majorallele or an allele that is the most frequently occurring allele. Theterm “variant” can in some embodiments refer to a minor allele or anallele that is not the most frequently occurring allele. In exemplaryembodiments, a capture probe set comprises a pair of probes, one ofwhich is selective for a major allele of the gene and one of which isselective for a minor allele of the gene. In some embodiments, a captureprobe set comprises more than two probes, each of which is selective fora different allele of the gene. In exemplary embodiments, a captureprobe set comprises one or more probes selective for one or more allelesof one or more genes.

In some embodiments, one or more capture probes are used to identify thebase at a detection position. In these embodiments, each different probecomprises a different base at an “interrogation position,” which willdifferentially hybridize to a base at the detection position of thetarget sequence. By using different probes, each with a different baseat the interrogation position, the identification of the base at thedetection position is elucidated.

In one embodiment, all nucleotides outside of the interrogation positionin two or more probes are the same as compared between the probes; thatis, in some embodiments it is preferable to use probes that have equalall components other than the interrogation position (e.g., both thelength of the probes as well as the non-interrogation bases) to allowgood discrimination. In some embodiments, it may be desirable to alterother components, in order to maximize discrimination at the detectionposition. For example, all nucleotides outside of the interrogationposition in two probes may be the same except for one or two nucleicacids added to the end of only one probe.

B. Oligonucleotides

The invention provides compositions comprising oligonucleotides forpracticing the detection and prediction methods of the invention. Theoligonucleotides typically are from 10 to 60 nucleotides in length. Insome embodiments, the oligonucleotide is about 45-60 nucleotides inlength. Each oligonucleotide is complementary to a target sequence ofinterest. In some embodiments, the oligonucleotide is complementary to atarget sequence of interest that comprises a SNP selected from the groupconsisting of the SNPs listed in Table 1. In some embodiments, theoligonucleotide is complementary to a target sequence of interest thatcomprises a SNP located in a gene selected from the group consisting ofDOCK2, F13A1, CD36, and PTPRR. In some embodiments, the oligonucleotideis complementary to a target sequence of interest that comprises a SNPselected from the group consisting of rs11744216, rs13206518, rs3211834,rs1863993, rs4147385, and rs1567748.

C. Diagnostic Kits

The invention also provides kits for carrying out the detection andprediction methods of the invention. The kits comprise at least one ormore allele-specific oligonucleotide for the SNP described in Table 1.Diagnostic kits for SNPs generally include means of identifying the SNP,e.g., oligonucleotides suitable for amplifying the SNP and directionsfor detection. Primers can be 10, 11, 12, 13, 14, 15, 16, 17, 18, 19,20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37,38, 39, 40, 50 or more nucleotides in length. The kits may includeseveral oligonucleotide sequences to detect at least one singlenucleotide polymorphism (SNP) of the invention, e.g., a firstoligonucleotide sequence and/or second and/or third and/or additionaloligonucleotides that detect at least one SNP selected from the groupconsisting of the SNPs listed in Table 1, the SNPs listed in Table 2,the SNPs listed in Table 3, and the SPNs listed in Table 4. Optionaladditional components of the kit include, for example, positive andnegative controls, restriction enzymes, reverse-transcriptase orpolymerase, the substrate nucleoside triphosphates, means used to label(for example, an avidinenzyme conjugate and enzyme substrate andchromogen if the label is biotin), and the appropriate buffers forreverse transcription, PCR, or hybridization reactions.

In some embodiments, the kits may include one or more oligonucleotidesequences to detect at least one SNP selected from the group consistingof rs11744216, rs13206518, rs3211834, rs1863993, rs4147385, andrs1567748.

In one embodiment, the present invention provides a diagnostic kit forpredicting the risk of developing antibodies against Factor VIII (FVIII)in an individual diagnosed with Hemophilia, the kit comprising at leastone oligonucleotide capable of being used to detect at least one singlenucleotide polymorphism (SNP) selected from the group consisting of aSNP listed in Table 1, a SNP listed in Table 2, a SNP listed in Table 3,and a SNP listed in Table 4. In a preferred embodiment, the at least oneSNP is selected from those listed in Table 3. In another preferredembodiment, the at least one SNP is selected from the group consistingof rs12368829, rs11744216, rs1863993, rs4147385, rs12546235, rs4242389,rs10054825, rs17535213, rs10072056, and rs17725712. In one embodiment,the oligonucleotide capable of being used to detect at least one SNPcomprises a sequence complementary to a genomic sequence flanking theSNP. In a specific embodiment, the oligonucleotide sequence that iscomplementary to the genomic sequence that flanks a SNP includes anucleotide corresponding to the position of the SNP in the genome. Inone embodiment, the nucleotide corresponding to the position of the SNPin the genome is the rare nucleotide (i.e., the SNP). In anotherembodiment, the nucleotide corresponding to the position of the SNP inthe genome is the wild type nucleotide.

In another embodiment, the present invention provides a diagnostic kitfor predicting the risk of developing antibodies against Factor VIII(FVIII) in an individual diagnosed with severe Hemophilia, the kitcomprising at least one oligonucleotide capable of being used to detectat least one single nucleotide polymorphism (SNP) selected from thegroup consisting of a SNP listed in Table 2 and a SNP listed in Table 4.In a preferred embodiment, the at least one SNP is selected from thoselisted in Table 4. In another preferred embodiment, the at least one SNPis selected from the group consisting of rs12368829, rs4147385,rs11744216, rs1863993, rs17535213, rs10072056, rs10054825, rs12546235,rs4242389, rs2071336, rs414634, rs17725712, rs11773821, rs8005905, andrs9482888. In one embodiment, the oligonucleotide capable of being usedto detect at least one SNP comprises a sequence complementary to agenomic sequence flanking the SNP. In a specific embodiment, theoligonucleotide sequence that is complementary to the genomic sequencethat flanks a SNP includes a nucleotide corresponding to the position ofthe SNP in the genome. In one embodiment, the nucleotide correspondingto the position of the SNP in the genome is the rare nucleotide (i.e.,the SNP). In another embodiment, the nucleotide corresponding to theposition of the SNP in the genome is the wild type nucleotide.

D. Oligonucleotide Arrays

The invention also provides assay compositions for use in solid phaseassays; such compositions can include, for example, one or morepolynucleotides of the invention immobilized on a solid support, and alabeling reagent. In each case, the assay compositions can also includeadditional reagents that are desirable for hybridization. In preferredembodiments, the solid phase assay is a microarray comprising a supporthaving a plurality of discrete regions, wherein each discrete regioncomprises one or more nucleic acid fragments spotted thereon. In someembodiments, the one or more nucleic acid fragments spotted on themicroarray support comprises a sequence that is complementary to a SNPselected from the group consisting of the SNPs listed in Table 1.

In one embodiment, the invention provides a microarray for predictingthe risk of developing antibodies against Factor VIII (FVIII) in anindividual diagnosed with Hemophilia, the microarray comprising asupport having a plurality of discrete regions, each discrete regionhaving a nucleic acid fragment spotted thereon, wherein at least onenucleic acid fragment spotted on the support comprises a sequence thatis complementary to a genomic sequence that flanks a single nucleotidepolymorphism (SNP) selected from the group consisting of a SNP listed inTable 1, a SNP listed in Table 2, a SNP listed in Table 3, and a SNPlisted in Table 4. In a preferred embodiment, the at least one SNP isselected from those listed in Table 3. In another preferred embodiment,the at least one SNP is selected from the group consisting ofrs12368829, rs11744216, rs1863993, rs4147385, rs12546235, rs4242389,rs10054825, rs17535213, rs10072056, and rs17725712. In one embodiment,the oligonucleotide capable of being used to detect at least one SNPcomprises a sequence complementary to a genomic sequence flanking theSNP. In a specific embodiment, the oligonucleotide sequence that iscomplementary to the genomic sequence that flanks a SNP includes anucleotide corresponding to the position of the SNP in the genome. Inone embodiment, the nucleotide corresponding to the position of the SNPin the genome is the rare nucleotide (i.e., the SNP). In anotherembodiment, the nucleotide corresponding to the position of the SNP inthe genome is the wild type nucleotide.

In certain embodiments, the microarray comprises at least 2 nucleic acidfragments comprising a sequence that is complementary to a genomicsequence that flanks a single nucleotide polymorphism (SNP) listed inTables 1 to 4, or at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51,52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69,70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87,88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104,105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118,119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132,133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146,147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160,161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174,175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188,189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202,203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216,217, 218, 219, 220, more, or all of the SNPs listed in Tables 1 to 4. Ina preferred embodiment, the SNPs are selected from those listed inTables 1 and 3. In another preferred embodiment, the SNPs are selectedfrom those listed in Table 3.

In one embodiment, the invention provides a microarray for predictingthe risk of developing antibodies against Factor VIII (FVIII) in anindividual diagnosed with Hemophilia, the microarray comprising asupport having a plurality of discrete regions, each discrete regionhaving a nucleic acid fragment spotted thereon, wherein at least onenucleic acid fragment spotted on the support comprises a sequence thatis complementary to a genomic sequence that flanks a single nucleotidepolymorphism (SNP) selected from the group consisting of a SNP listed inTable 2 and a SNP listed in Table 4. In a preferred embodiment, the atleast one SNP is selected from those listed in Table 4. In anotherpreferred embodiment, the at least one SNP is selected from the groupconsisting of rs12368829, rs4147385, rs11744216, rs1863993, rs17535213,rs10072056, rs10054825, rs12546235, rs4242389, rs2071336, rs414634,rs17725712, rs11773821, rs8005905, and rs9482888. In one embodiment, theoligonucleotide capable of being used to detect at least one SNPcomprises a sequence complementary to a genomic sequence flanking theSNP. In a specific embodiment, the oligonucleotide sequence that iscomplementary to the genomic sequence that flanks a SNP includes anucleotide corresponding to the position of the SNP in the genome. Inone embodiment, the nucleotide corresponding to the position of the SNPin the genome is the rare nucleotide (i.e., the SNP). In anotherembodiment, the nucleotide corresponding to the position of the SNP inthe genome is the wild type nucleotide.

In certain embodiments, the microarray comprises at least 2 nucleic acidfragments comprising a sequence that is complementary to a genomicsequence that flanks a single nucleotide polymorphism (SNP) listed inTables 2 and 4, or at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51,52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69,70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87,88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104,105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118,119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132,133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146,147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160,161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174,175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188,189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202,203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216,217, 218, 219, 220, more, or all of the SNPs listed in Tables 1 to 4. Ina preferred embodiment, the SNPs are selected from those listed in Table3.

V. Specific Embodiments

In one embodiment, the present invention provides a method forpredicting the risk of developing antibodies against Factor VIII (FVIII)in an individual diagnosed with Hemophilia, the method comprising thesteps of: (a) detecting the presence of at least one single nucleotidepolymorphism (SNP) selected from the group consisting of a SNP listed inTable 1, a SNP listed in Table 2, a SNP listed in Table 3, and a SNPlisted in Table 4, in a biological sample from the individual; and (b)predicting the risk of the individual of developing antibodies to FVIII.

In one embodiment, the present invention provides a method forpredicting the risk of developing antibodies against Factor VIII (FVIII)in an individual diagnosed with Hemophilia, the method comprising thesteps of: (a) detecting the presence of at least one single nucleotidepolymorphism (SNP) selected from the group consisting of a SNP listed inTable 1, a SNP listed in Table 2, a SNP listed in Table 3, and a SNPlisted in Table 4, in a biological sample from the individual; and (b)predicting the risk of the individual of developing antibodies to FVIII,wherein the detection of a SNP associated with an odds ratio of lessthan 1 is predictive of a decreased risk of developing antibodiesagainst FVIII and the detection of a SNP associated with an odds ratioof more than 1.0 is predictive of an increased risk of developingantibodies against FVIII.

In one embodiment of the methods provided above, the individual has notreceived therapy comprising administration of FVIII.

In one embodiment of the methods provided above, the individual hasreceived therapy comprising administration of FVIII.

In one embodiment of the methods provided above, the individual has beendiagnosed with mild Hemophilia.

In one embodiment of the methods provided above, the individual has beendiagnosed with moderate Hemophilia.

In one embodiment of the methods provided above, the individual has beendiagnosed with severe Hemophilia.

In one embodiment of the methods provided above, the at least one singlenucleotide polymorphism (SNP) is a SNP listed in Table 2 or a SNP listedin Table 4.

In one embodiment of the methods provided above, the step of detectingthe presence of at least one SNP comprises amplifying a nucleic acidpresent in the biological sample.

In one embodiment of the methods provided above, the step of detectingthe presence of at least one SNP comprises a technique selected from thegroup consisting of mass spectroscopy, RT-PCR, microarray hybridization,pyrosequencing, thermal cycle sequencing, capillary array sequencing,and solid phase sequencing.

In one embodiment of the methods provided above, the step of detectingthe presence of at least one SNP comprises a methods selected from thegroup consisting of a hybridization-based method, an enzymatic-basedmethod, a PCR-based method, a sequencing method, a ssDNA conformationalmethod, and a DNA melting temperature assay.

In one embodiment of the methods provided above, the step of detectingthe presence of at least one SNP comprises comprises microarrayhybridization.

In one embodiment of the methods provided above, the SNP is selectedfrom the group consisting of rs12368829, rs11744216, rs1863993,rs4147385, rs12546235, rs4242389, rs10054825, rs17535213, rs10072056,and rs17725712.

In one embodiment of the methods provided above, at least one detectedSNP is rs12368829.

In one embodiment of the methods provided above, at least one detectedSNP is rs11744216.

In one embodiment of the methods provided above, at least one detectedSNP is rs1863993.

In one embodiment of the methods provided above, at least one detectedSNP is rs4147385.

In one embodiment of the methods provided above, at least one detectedSNP is rs12546235.

In one embodiment of the methods provided above, at least one detectedSNP is rs4242389.

In one embodiment of the methods provided above, at least one detectedSNP is rs10054825.

In one embodiment of the methods provided above, at least one detectedSNP is rs17535213.

In one embodiment of the methods provided above, at least one detectedSNP is rs10072056.

In one embodiment of the methods provided above, at least one detectedSNP is rs17725712.

In one embodiment of the methods provided above, the SNP is selectedfrom the group consisting of rs12368829, rs4147385, rs11744216,rs1863993, rs17535213, rs10072056, rs10054825, rs12546235, rs4242389,rs2071336, rs414634, rs17725712, rs11773821, rs8005905, and rs9482888.

In one embodiment of the methods provided above, at least one detectedSNP is rs12368829.

In one embodiment of the methods provided above, at least one detectedSNP is rs4147385.

In one embodiment of the methods provided above, at least one detectedSNP is rs11744216.

In one embodiment of the methods provided above, at least one detectedSNP is rs1863993.

In one embodiment of the methods provided above, at least one detectedSNP is rs17535213.

In one embodiment of the methods provided above, at least one detectedSNP is rs10072056.

In one embodiment of the methods provided above, at least one detectedSNP is rs10054825.

In one embodiment of the methods provided above, at least one detectedSNP is rs12546235.

In one embodiment of the methods provided above, at least one detectedSNP is rs4242389.

In one embodiment of the methods provided above, at least one detectedSNP is rs2071336.

In one embodiment of the methods provided above, at least one detectedSNP is rs414634.

In one embodiment of the methods provided above, at least one detectedSNP is rs17725712.

In one embodiment of the methods provided above, at least one detectedSNP is rs11773821.

In one embodiment of the methods provided above, at least one detectedSNP is rs8005905.

In one embodiment of the methods provided above, at least one detectedSNP is rs9482888.

In one embodiment of the methods provided above, the method furthercomprises assigning a treatment to the individual based on the predictedrisk of developing antibodies against Factor VIII.

In one embodiment of the methods provided above, the treatment comprisesadministration of Factor VIII.

In one embodiment of the methods provided above, the treatment comprisesadministration of a non-Factor VIII hemostatic agent.

In one embodiment of the methods provided above, the treatment comprisesadministration of Factor VIII and a non-Factor VIII hemostatic agent.

In one embodiment of the methods provided above, the treatmentcomprising administration of Factor VIII is assigned to an individualwith a predicted decreased risk of developing antibodies against FactorVIII.

In one embodiment of the methods provided above, the treatmentcomprising Factor VIII bypass therapy is assigned to an individual witha predicted increased risk of developing antibodies against Factor VIII.

In one embodiment of the methods provided above, assigning treatmentcomprises adjusting a dosage and/or frequency of Factor VIIIadministration based on the predicted risk of developing antibodiesagainst Factor VIII.

In one embodiment of the methods provided above, adjusting a dosage ofFactor VIII comprises increasing the dosage and/or frequency of FactorVIII administered to an individual with a predicted decreased risk ofdeveloping antibodies against Factor VIII.

In one embodiment of the methods provided above, adjusting a dosage ofFactor VIII comprises decreasing the dosage and/or frequency of FactorVIII administered to an individual with a predicted increased risk ofdeveloping antibodies against Factor VIII.

In one embodiment of the methods provided above, assigning treatmentcomprises adjusting a dosage and/or frequency of a non-Factor VIIIhemostatic agent administration based on the predicted risk ofdeveloping antibodies against Factor VIII.

In one embodiment of the methods provided above, adjusting a dosage of anon-Factor VIII hemostatic agent comprises decreasing the dosage and/orfrequency of a non-Factor VIII hemostatic agent administered to anindividual with a predicted decreased risk of developing antibodiesagainst Factor VIII.

In one embodiment of the methods provided above, adjusting a dosage of anon-Factor VIII hemostatic agent comprises increasing the dosage and/orfrequency of a non-Factor VIII hemostatic agent administered to anindividual with a predicted increased risk of developing antibodiesagainst Factor VIII.

In one embodiment, the present invention provides an oligonucleotidefrom 10 to 60 nucleotides in length that contacts at least one singlenucleotide polymorphism (SNP) selected from the group consisting of theSNPs listed in Table 1.

In one embodiment, the present invention provides a diagnostic kit forpredicting the risk of developing antibodies against Factor VIII (FVIII)in an individual diagnosed with Hemophilia, the kit comprising at leastone oligonucleotide capable of being used to detect at least one singlenucleotide polymorphism (SNP) selected from the group consisting of aSNP listed in Table 1, a SNP listed in Table 2, a SNP listed in Table 3,and a SNP listed in Table 4.

In one embodiment of the diagnostic kits described above, the SNP isselected from the group consisting of rs12368829, rs11744216, rs1863993,rs4147385, rs12546235, rs4242389, rs10054825, rs17535213, rs10072056,and rs17725712.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs12368829.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs11744216.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs1863993.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs4147385.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs12546235.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs4242389.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs10054825.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs17535213.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs10072056.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs17725712.

In one embodiment, the present invention provides a diagnostic kit forpredicting the risk of developing antibodies against Factor VIII (FVIII)in an individual diagnosed with severe Hemophilia, the kit comprising atleast one oligonucleotide capable of being used to detect at least onesingle nucleotide polymorphism (SNP) selected from the group consistingof a SNP listed in Table 2 and a SNP listed in Table 4.

In one embodiment of the diagnostic kits described above, the SNP isselected from the group consisting of rs12368829, rs4147385, rs11744216,rs1863993, rs17535213, rs10072056, rs10054825, rs12546235, rs4242389,rs2071336, rs414634, rs17725712, rs11773821, rs8005905, and rs9482888.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs12368829.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs4147385.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs11744216.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs1863993.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs17535213.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs10072056.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs10054825.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs12546235.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs4242389.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs2071336.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs414634.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs17725712.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs11773821.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs8005905.

In one embodiment of the diagnostic kits described above, the kitcomprises an oligonucleotide capable of being used to detect SNPrs9482888.

In one embodiment of the diagnostic kits described above, theoligonucleotide flanks the position of the SNP in the genome.

In one embodiment of the diagnostic kits described above, theoligonucleotide overlaps the position of the SNP in the genome.

In one embodiment, the present invention provides a microarray forpredicting the risk of developing antibodies against Factor VIII (FVIII)in an individual diagnosed with Hemophilia, the microarray comprising asupport having a plurality of discrete regions, each discrete regionhaving a nucleic acid fragment spotted thereon, wherein at least onenucleic acid fragment spotted on the support comprises a sequence thatis complementary to a genomic sequence that flanks a single nucleotidepolymorphism (SNP) selected from the group consisting of a SNP listed inTable 1, a SNP listed in Table 2, a SNP listed in Table 3, and a SNPlisted in Table 4.

In one embodiment of the microarrays described above, the SNP isselected from the group consisting of rs12368829, rs11744216, rs1863993,rs4147385, rs12546235, rs4242389, rs10054825, rs17535213, rs10072056,and rs17725712.

In one embodiment, the present invention provides a microarray forpredicting the risk of developing antibodies against Factor VIII (FVIII)in an individual diagnosed with severe Hemophilia, the microarraycomprising a support having a plurality of discrete regions, eachdiscrete region having a nucleic acid fragment spotted thereon, whereinat least one nucleic acid fragment spotted on the support comprises asequence that is complementary to a genomic sequence that flanks asingle nucleotide polymorphism (SNP) selected from the group consistingof a SNP listed in Table 2 and a SNP listed in Table 4.

In one embodiment of the microarrays described above, the SNP isselected from the group consisting of rs12368829, rs4147385, rs11744216,rs1863993, rs17535213, rs10072056, rs10054825, rs12546235, rs4242389,rs2071336, rs414634, rs17725712, rs11773821, rs8005905, and rs9482888.

In one embodiment of the microarrays described above, the sequence thatis complementary to a genomic sequence that flanks a single nucleotidepolymorphism (SNP) includes a nucleotide corresponding to the positionof the SNP in the genome.

VI. Examples Example 1

The following example is offered to illustrate, but not to limit, theclaimed invention.

Through a collaboration among three multi-center studies: the HemophiliaInhibitor Genetics Study (HIGS), the Malmo International Brother Study(MIBS), and the Hemophilia Growth and Development Study (HGDS), acombined cohort was formed to conduct an association study to test thehypothesis that antibody development to FVIII is mediated by immuneresponse and immune modifier genes. The RIGS study population (N=295)was composed of brother pairs concordant for a history of inhibitors, ordiscordant (one with an inhibitor, the other without); and a group ofsingletons with inhibitors. Participants from Europe and North Americaaccounted for 43% and 57% of the HIGS population, respectively. The MIBSstudy population (N=120) was composed of brother pairs with hemophiliawith or without inhibitors, recruited primarily from centers in Europe.The HGDS (N=265) is a population-based longitudinal investigationconducted in 14 US hemophilia treatment centers. Together, these studiesmake up the HIGS Combined Cohort and included clinical and laboratorydata for 680 people with hemophilia A.

Using the Illumina iSelect® platform, 14,626 single nucleotidepolymorphisms (SNPs) from 1,081 genes were typed. These genes includedimmune response and immune modifier genes, including cytokines and theirreceptors, chemokines and their receptors, pathway gene involved ininflammatory and immune responses, and human leukocyte antigen (HLA)gene complex genes. The SNPs were selected using an algorithm tomaximize information content and minimize the number of SNPs/gene. Allregulatory and nonsynonymous (codon-changing) SNPs within a gene werechosen, as well as haplotype tagging SNPs, using stringent criteria toavoid SNPs that are non-independent.

The statistical analysis was completed among the total group (N=680).Models were adjusted for population substructure, severity ofhemophilia, type of factor VIII gene mutation (high vs. low risk), yearof birth, and geographic region (Europe/North America). Meta-analyseswere used to obtain single odds ratios (OR) and p-values for the threecohorts.

Eighty-five percent of the HIGS Combined Cohort had severe (<0.01 IU/mL)hemophilia; 10% had moderate (0.01-0.05 IU/mL) hemophilia; and 4.4% hadmild (>0.05-0.4 IU/mL) hemophilia. The cohort was predominately ofEuropean descent, 81.0%, with 6.2% of African descent, 8.8% Hispanic,and the remaining 4% of other races and ethnicities. Forty-nine percentof the cohort had, or had a history of, an inhibitor ≧1 BU.

A total of 13,952 of the 14,626 (95.4%) SNPs were successfullygenotyped. One hundred fourteen were associated with inhibitor status atthe p<0.01 level (Table 1). Strong SNP associations for the total groupwere observed in the DOCK2 (rs11744216, OR 0.28, p=0.00004; andrs1863993, OR 3.9, p=0.0002), MAPK9 (rs4147385, OR 2.0, p=0.0003), F13A1(rs13206518, OR 0.32, p=0.00007), CD36 (rs3211834, OR 0.56, p=0.0002),and PTPRR (rs1567748, OR 0.51, p=0.0003) genes (Table 1). For fourmarkers located within the MAPK9 (rs4147385), DOCK2 (rs11744216 andrs1863993), and CD36 (rs3211834) genes, the associations were similar,or stronger, for the subgroup with severe hemophilia (Table 2). For thesubgroup with severe hemophilia, a strong association with inhibitordevelopment was found for the SNP rs4147385, a C>T variant in anintronic region of the MAPK9 gene (OR 2.3, p=0.00003); for the SNPrs11744216, a C>G variant in an intronic region of the DOCK2 gene (OR0.30, p=0.00008); for the SNP rs1863993, a C>T variant in an intronicregion of the DOCK2 gene (OR 4.4, p=0.0009); and for the SNP rs3211834,a A>C variant in an intronic region of the CD36 gene (OR 0.59,p=0.0008).

Example 2

In order to further validate the findings in Example 1, additionalsamples were collected and analyzed for the presence of SNPs associatedwith the formation of Factor VIII autoantibody inhibitors in patientswith mild, moderate, and severe Hemophilia. As above, a combined cohortwas formed from three multi-center studies: the Hemophilia InhibitorGenetics Study (HIGS), the Malmo International Brother Study (MIBS), andthe Hemophilia Growth and Development Study (HGDS), to conduct anassociation study to test the hypothesis that antibody development toFVIII is mediated by immune response and immune modifier genes. Intotal, samples from 774 patients diagnosed with Hemophilia, 674 of whichwere diagnosed with severe Hemophilia, were used for the meta-analysis.

Using the Illumina iSelect® platform, 14,626 single nucleotidepolymorphisms (SNPs) from 1,081 genes were typed. These genes includedimmune response and immune modifier genes, including cytokines and theirreceptors, chemokines and their receptors, pathway gene involved ininflammatory and immune responses, and human leukocyte antigen (HLA)gene complex genes. The SNPs were selected using an algorithm tomaximize information content and minimize the number of SNPs/gene. Allregulatory and nonsynonymous (codon-changing) SNPs within a gene werechosen, as well as haplotype tagging SNPs, using stringent criteria toavoid SNPs that are non-independent.

Genotype data were obtained for the entire, combined cohort on theIllumina iSelect panel composed of 14,626 polymorphic markers. Testingfor missingness (>20% missing), low minor allele frequency (<0.01) and adeparture from Hardy Weinburg equilibrium (p<0.001), left 13,394 markersfor analysis. The analysis was carried out separately for each of thethree study cohorts; HGDS, MIBS and HIGS. Using the markers that passedQC, principal components were constructed to account for populationadmixture. Because of the different distributions of related individualsin each cohort, different models were used to analyze the data. The HGDSindividuals were analyzed with logistic regression, MBS with GEE andHIGS with alternating logistic regression. Covariates included severityof hemophilia, year of birth, the first three principal components toaccount for admixture, and mutation risk in the case of MIBS and HIGSand an indicator of presence of factor VIII gene inversion for HGDS. Theprimary hypothesis test was carried out on the predictor for each SNPwhich was modeled as additive or specifically the number of minoralleles in each individual. Additionally the models were rerun on onlythe individuals with severe hemophilia. Once each estimate and standarderror was obtained for each cohort model on each SNP, they were combinedin a meta analytic technique summing the estimates weighted by thestandard errors. A new standard error was also calculated which allowedZ statistic to be constructed and tested for the total combined cohort.

The statistical analysis was completed among the total group (N=774), aswell as among patients diagnosed with severe Hemophilia (N=674). Modelswere adjusted for population substructure, severity of hemophilia, typeof factor VIII gene mutation (high vs. low risk), year of birth, andgeographic region (Europe/North America). Meta-analyses were used toobtain single odds ratios (OR) and p-values for the three cohorts.

A total of 13,394 of the 14,626 (91.6%) SNPs were successfullygenotyped. Two hundred and sixteen were associated with inhibitor statusat the p<0.01 level (Table 3). Strong

SNP associations for the total group were observed in the CCDC41(rs12368829, OR 0.27, p=5.08E-07); DOCK2 (rs11744216, OR 0.31,p=3.56E-06; and rs1863993, OR 3.89, p=8.36E-05); MAPK9 (rs4147385, OR2.14, p=9.22E-06); TNFRSF10C (rs12546235, OR 0.43, p=1.11E-05; andrs4242389, OR 0.50, p=0.000113642); IQGAP2 (rs10054825, OR 0.37,p=2.21E-05); PUS7L (rs17535213, OR 0.57, p=4.02E-05); PDGFRB(rs10072056, OR 0.61, p=5.84E-05); and CSF1R (rs17725712, OR 2.51,p=0.000165351) genes.

Strong SNP associations for the severe Hemophilia group were observed inthe CCDC41 (rs12368829, OR 0.25, p=1.81E-07); MAPK9 (rs4147385, OR 2.44,p=1.08E-06); DOCK2 (rs11744216, OR 0.32, p=5.86E-06; and rs1863993, OR4.33, p=0.000159); PUS7L (rs17535213, OR 0.54, p=1.04E-05); PDGFRB(rs10072056, OR 0.57, p=1.05E-05); IQGAP2 (rs10054825, OR 0.37,p=1.10E-05); TNFRSF10C (rs12546235, OR 0.44, p=1.64E-05; and rs4242389,OR 0.50, p=0.000128788); TNFRSF17 (rs2071336, OR 0.27, p=0.000106); BLM(rs414634, OR 1.72, p=0.000124); CSF1R (rs17725712, OR 3.00,p=0.000124); PTPRN2 (rs11773821, OR 0.51, p=0.000130); HSP90AA1(rs8005905, OR 0.48; p=0.000132); and PTPRK (rs9482888, OR 10.75,p=0.000182) genes.

Example 3

The risk of developing antibodies against Factor VIII (FVIII) in anindividual diagnosed with Hemophilia A may be determined by detectingone or more SNPs disclosed herein. To do this, a capture probe setcomprising oligonucleotides capable of distinguishing the nucleotidepresent at the SNP position may be attached to a solid support to createan oligonucleotide array. For example, probes capable of detecting theset of SNPs listed in Table 5 are used to create a microarray. Nucleicacid (i.e., genomic DNA, cDNA, mRNA, etc.) is isolated and/or amplifiedfrom a biological sample taken from the individual and subsequentlyhybridized to the array using hybridization techniques well known in theart. The identity of the nucleotides present at the 24 SNP genomicpositions shown in Table 5 can then be determined usingdetection/analysis techniques also well known in the art. Alternatively,the presence or absence of the SNP of interest can be determined usingthe same well known techniques.

The results of the SNP detection described above, can then be used topredict a risk for the development of Factor VIII inhibitor antibodiesin the individual. For example, the detection of rs12368829 in thesample is predictive of a significantly decreased risk of developingFactor VIII inhibitors. Similarly, the detection of both rs4147385 andrs927335 is predictive of a significantly incresed risk of developingFactor VIII inhibitors.

Likewise, detection of one or more SNPs listed in Table 5 may beachieved by performing one or more RT-qPCR reactions. In this case,individual RT-qPCR reactions or multiplex RT-qPCR reactions may beperformed to identify the nucleotides present at the genomic locationsof the SNPs listed in Table 5, or to detect the presence or absence ofthe SNPs listed in Table 5, using techniques well known in the art. Thedata provided by these assays may then be used to provide a risk for thedevelopment of Factor VIII inhibitor antibodies in the individual.

Any probe set may be used, comprising capture probes capable ofdetecting between 1 and all of the SNPs listed in Tables 1 to 4. Theprobe sets may further comprise internal controls, additional probesuseful for providing further predictive power, and/or unrelated probesets.

TABLE 5 SNP Gene Meta Odds Meta P rs12368829 CCDC41 0.27311013 5.08E−07rs11744216 DOCK2 0.30667899 3.56E−06 rs4147385 MAPK9 2.13745578 9.22E−06rs12546235 TNFRSF10C 0.43388002 1.11E−05 rs10054825 IQGAP2 0.37435472.21E−05 rs17535213 PUS7L 0.57027044 4.02E−05 rs10072056 PDGFRB0.60837768 5.84E−05 rs1863993 DOCK2 3.88981038 8.36E−05 rs4242389TNFRSF10C 0.49632251 0.00011364 rs17725712 CSF1R 2.50759989 0.00016535rs11773821 PTPRN2 0.54041127 0.00033105 rs414634 BLM 1.622462050.00033946 rs1882019 HSP90B1 0.53629298 0.00034044 rs13206518 F13A10.39427174 0.00035099 rs927335 CD44 1.69891458 0.00036195 rs6482644PTPRE 0.57798945 0.00040403 rs4077341 TNFRSF10C 0.63448794 0.00042665rs1884564 LOC728018 0.55434198 0.00051894 rs3826392 MAP2K4 0.63098390.00053597 rs390406 CLC 0.56597223 0.00053686 rs440238 PTPRD 0.620081210.00057369 rs9482888 PTPRK 6.50375409 0.00058077 rs2596606 NFATC11.75806233 0.00058124 rs17652304 IQGAP2 3.55426184 0.00062941

Example 4

The results obtained in the previous example may then be used to director modify a course of therapy in the individual. For example, thedetection of SNP rs12368829, which is predictive of a decreasedlikelihood of the development of Factor VIII inhibitor in response toFactor VIII therapy, may lead a physician to assign a course oftreatment comprising administration of FVIII to the individual.Conversely, the detection of SNPs rs4147385 and rs927335, which ispredictive of an increased risk of developing Factor VIII inhibitorantibodies in response to Factor VIII therapy, may lead a physician toassign a course of treatment comprising administration of a non-FVIIIhemostatic agent (i.e., FVIII bypass therapy). Alternatively, after thedetection of both rs4147385 and rs927335, a physician may assign acourse of treatment comprising administration of both Factor VIII and anon-FVIII hemostatic agent. In this manner, combination therapy may moreeffective than administration of either Factor VIII or a non-FVIIIhemostatic agent alone. For example, the development of anti-FVIIIinhibitory antibodies results in the reduced efficacy of FVIIIadministration, at which point the non-FVIII hemostatic agent maysupplement this deficiency.

Although the foregoing invention has been described in some detail byway of illustration and example for purposes of clarity ofunderstanding, one of skill in the art will appreciate that certainchanges and modifications may be practiced within the scope of theappended claims. In addition, each reference provided herein isincorporated by reference in its entirety to the same extent as if eachreference was individually incorporated by reference. Where a conflictexists between the instant application and a reference provided herein,the instant application shall dominate.

TABLE 1 SNP Chrom BP Region Gene HGDS Odds HGDS P rs11744216 5 169018841intron DOCK2 0.4264463 0.170966 rs13206518 6 6098001 intron F13A10.759322 0.616534 rs2227827 5 76054800 intron F2R 1.2382572 0.711259rs3211834 7 80118053 intron CD36 0.6593762 0.138659 rs1863993 5169142758 intron DOCK2 5.0476821 0.011274 rs910682 6 112282428 intronFYN 2.1062593 0.012895 rs4147385 5 179610123 intron MAPK9 2.90879570.000155 rs1567748 12 69360997 intron PTPRR 1.0194855 0.95761 rs32118217 80116499 intron CD36 0.6553039 0.126315 rs6482644 10 129715311 intronPTPRE 0.6295681 0.08468 rs414634 15 89157257 intron BLM 1.91527080.012981 rs10072056 5 149485499 intron PDGFRB 1.0238421 0.931546rs17652304 5 75912949 intron IQGAP2 4.5248878 0.005062 rs2584019 1269318052 locus-region PTPRR 1.1113653 0.767548 rs2879097 17 34143085locus-region PCGF2 0.3989738 0.01103 rs17725712 5 149471001 intron CSF1R2.2707005 0.092905 rs12667537 7 157343101 intron PTPRN2 0.52852060.026763 rs2302821 9 131541702 mrna-utr PTGES 0.413199 0.079245 rs4104 7157639794 intron PTPRN2 0.7155353 0.197892 rs6837303 4 111189034locus-region ELOVL6 0.5807509 0.058419 rs3736395 5 75924224 intronIQGAP2 2.0624196 0.014235 rs12546235 8 23018464 intron TNFRSF10C0.7274756 0.422086 rs4698806 4 111190938 mrna-utr ELOVL6 0.56646350.050564 rs11952962 5 75931035 intron IQGAP2 2.0142888 0.017929rs3797390 5 75942821 intron IQGAP2 2.3878022 0.002205 rs13042473 2040843315 intron PTPRT 0.5586063 0.107265 rs13096099 3 61819146 intronPTPRG 0.4982842 0.234687 rs7290696 22 30671684 intron YWHAH 1.24901020.459588 rs949664 12 69368222 intron PTPRR 1.0767496 0.809522 rs446225110 129749982 intron PTPRE 0.7208544 0.185484 rs4752894 11 48077512intron PTPRJ 0.5295218 0.020616 rs10261447 7 157643166 intron PTPRN20.7552154 0.278122 rs7246376 19 8109328 coding- FBN3 1.4043985 0.260212nonsynonymous rs4752896 11 48086525 intron PTPRJ 3.8641862 0.003824rs390406 19 44920811 locus-region CLC 0.6675452 0.239964 rs2596606 1875263804 intron NFATC1 1.8412808 0.05504 rs440238 9 9006071 intron PTPRD0.3654781 0.001385 rs1892803 3 37572487 intron ITGA9 1.9891348 0.067518rs4077341 8 23018293 intron TNFRSF10C 0.6342569 0.090988 rs9826296 339279822 locus-region CX3CR1 0.3438183 0.018361 rs7348444 20 40263638intron PTPRT 0.6379987 0.214628 rs4752904 11 48122843 coding- PTPRJ0.5229615 0.015662 nonsynonymous rs2305340 12 7157242 — — 0.4257190.037702 rs805274 6 31773173 intron BAT5 0.5365861 0.046424 rs1411479 1179273553 intron MR1 1.4273583 0.16464 rs2076620 1 29488905 intron PTPRU1.5037749 0.156645 rs4724231 7 43608739 intron STK17A 0.7894051 0.512999rs7715375 5 146106438 intron PPP2R2B 1.1146267 0.739882 rs7289754 2220926259 — — 2.2927241 0.00152 rs12310405 12 69330069 intron PTPRR1.0252831 0.929397 rs3845422 1 179279594 intron MR1 0.5959129 0.098555rs17671456 8 22441022 intron PPP3CC 1.5913304 0.206536 rs1885831 2040836321 intron PTPRT 0.6323805 0.213699 rs4472605 9 34556190 intronCNTFR 2.3112244 0.015115 rs5743740 23 12801881 intron TLR7 1.71030530.03429 rs2070123 1 78888493 coding- IFI44 0.8374258 0.666134nonsynonymous rs2179694 6 128405416 intron PTPRK 2.6815501 0.004271rs6782288 3 61805637 intron PTPRG 0.2706226 0.084428 rs1877563 339279468 locus-region CX3CR1 0.4255593 0.062242 rs1781795 6 6186280intron F13A1 1.846775 0.054544 rs9862163 3 37557606 intron ITGA91.8809113 0.073469 rs1882019 12 102861797 intron HSP90B1 0.59219780.25287 rs704853 1 165735488 intron CD247 2.4731734 0.006262 rs2278324 538917360 intron OSMR 2.4191263 0.008917 rs10854166 19 18513844 intronFKBP8 1.0554308 0.82636 rs7692976 4 111131016 intron EGF 0.84101740.490258 rs1046780 11 77604417 mrna-utr GAB2 0.634111 0.164847 rs712427511 48118881 intron PTPRJ 0.7740908 0.310137 rs1007212 15 97101441 intronIGF1R 1.6260816 0.052845 rs4498385 6 128491712 intron PTPRK 2.1345540.03148 rs3788151 21 45161993 intron ITGB2 0.6014832 0.293327 rs117402985 149472648 locus-region PDGFRB 1.1785056 0.58352 rs3815003 15 89113827intron BLM 0.7320953 0.32305 rs6482647 10 129716363 intron PTPRE0.8763896 0.590518 rs2296449 1 117380273 intron IGSF2 0.2786922 0.231422rs5746154 3 12680048 intron RAF1 0.7424757 0.425298 rs2020902 1 15706947intron CASP9 1.5643264 0.205653 rs927010 6 112254016 intron FYN0.9174485 0.759767 rs5743220 11 43299463 intron API5 0.8074122 0.59914rs499205 11 125639829 intron SRPR 0.3215836 0.001716 rs2302267 2312795499 intron TLR7 1.9061049 0.014414 rs6214 12 101317699 mrna-utrIGF1 1.5377377 0.088519 rs1105238 1 159948285 intron FCRLA 1.57230550.087345 rs12881815 14 63674348 coding- SYNE2 4.7576862 0.005158nonsynonymous rs10054825 5 75837339 intron IQGAP2 0.4214185 0.06373rs10836342 11 35198213 intron CD44 1.4258451 0.198951 rs3819496 8143920893 intron GML 0.7566059 0.292013 rs12831813 12 69338568 intronPTPRR 1.2079285 0.529818 rs2157605 6 30562055 — — 0.6308068 0.158206rs9487735 6 112272269 intron FYN 1.7518657 0.172178 rs9817149 3191740949 intron IL1RAP 2.3935609 0.044972 rs731305 7 157375601 intronPTPRN2 1.3532686 0.218857 rs304839 3 30706286 intron TGFBR2 1.75598480.05877 rs10406354 19 59022044 — — 0.8293457 0.602779 rs17763453 173664884 intron C17orf85 1.9012346 0.019355 rs2569190 5 139993100 intronCD14 1.5335318 0.093723 rs6476985 9 5507559 intron PDCD1LG2 1.75551370.101125 rs31519 5 135314336 intron LECT2 1.793477 0.019369 rs1267843 66191983 intron F13A1 0.7214938 0.204877 rs766502 12 9799696 intron CD690.4224928 0.03055 rs8064821 17 73868986 — — 1.6573297 0.157191 rs46460771 15699723 intron CASP9 1.4654677 0.204825 rs7851161 9 35234061 intronUNC13B 1.3813911 0.201171 rs1983165 3 62059196 intron PTPRG 0.81171570.496419 rs10074391 5 149486896 intron PDGFRB 1.3843383 0.4834 rs717091915 89115963 intron BLM 0.7391559 0.316431 rs4251520 12 42461605 intronIRAK4 1.1681216 0.665273 rs1465073 12 51979670 locus-region PFDN50.6281323 0.0735 rs613613 9 9004274 intron PTPRD 0.2400912 0.000257rs2298877 14 101617977 intron HSP90AA1 0.7034122 0.323878 rs17815972 310223974 intron IRAK2 0.6933789 0.131179 rs12810163 12 9872429 intronKLRF1 1.5092501 0.105882 rs2267908 20 1857920 intron SIRPA 1.68357460.046786 rs7099752 10 129641321 intron PTPRE 0.8058936 0.539731 SNP HIGSOdds HIGS P MIBS Odds MIBS P Meta Odds Meta P rs11744216 0.225712380.000282 0.3741365 0.301173 0.2792436 4.09E−05 rs13206518 0.381179280.028779 0.1181848 3.97E−05 0.32286804 6.93E−05 rs2227827 2.826649830.325022 5.7021018 3.60E−05 3.29946791 0.000226 rs3211834 0.51076960.003251 0.5661763 0.114955 0.5633609 0.000238 rs1863993 1.869962360.560579 3.9882943 0.006879 3.94139298 0.000247 rs910682 2.147471160.01239 1.5283489 0.310709 1.98915377 0.000261 rs4147385 2.388916210.009361 0.6891928 0.34438 1.96583851 0.000311 rs1567748 0.455654760.00219 0.2252939 0.002164 0.50890627 0.000327 rs3211821 0.522498960.004779 0.6143155 0.168962 0.57915491 0.000447 rs6482644 0.804147840.331749 0.2230707 2.88E−05 0.58402944 0.000508 rs414634 2.127056580.003435 0.9393436 0.851875 1.70382924 0.000785 rs10072056 0.544599050.006629 0.4262574 0.006412 0.62104044 0.001428 rs17652304 1.581790170.532079 3.7192948 0.073342 3.26828251 0.001504 rs2584019 0.524727230.010479 0.1747444 0.000521 0.55367097 0.001599 rs2879097 0.58834620.018123 0.8975647 0.765856 0.59218611 0.001635 rs17725712 1.891335130.146031 2.3052404 0.024417 2.15670137 0.001637 rs12667537 0.686161250.098587 0.5572059 0.10502 0.60851609 0.001786 rs2302821 0.506022430.027969 0.4440663 0.202565 0.47427361 0.001918 rs4104 0.611918330.023089 0.5689053 0.099584 0.63498198 0.002123 rs6837303 0.660233230.071935 0.5408342 0.102554 0.61144675 0.002241 rs3736395 1.541511510.165489 1.6901581 0.177493 1.76976249 0.002276 rs12546235 0.43201720.004881 0.2265523 0.175241 0.4990938 0.00229 rs4698806 0.68008160.092123 0.4841033 0.076412 0.6080967 0.002331 rs11952962 1.532523910.160159 1.72391 0.150491 1.75194031 0.002334 rs3797390 1.173416030.499644 1.680531 0.076666 1.59756682 0.002391 rs13042473 0.619339940.084364 0.5181073 0.054693 0.57273836 0.00244 rs13096099 0.296319210.006238 0.4908602 0.565263 0.36386724 0.002461 rs7290696 2.314796090.008075 1.7904536 0.075126 1.71913266 0.002555 rs949664 0.471284130.003215 0.4132124 0.023529 0.59591265 0.002641 rs4462251 0.551525930.006524 0.8004433 0.44484 0.65622124 0.002769 rs4752894 0.713896670.138587 0.5921131 0.159352 0.62569985 0.002927 rs10261447 0.609579150.021807 0.5689053 0.099584 0.6451481 0.002956 rs7246376 2.024404790.024548 2.4037715 0.063497 1.78756484 0.002991 rs4752896 1.668039370.267218 1.7183641 0.283547 2.24773698 0.003155 rs390406 0.363551890.000972 1.1098003 0.818363 0.55485629 0.003241 rs2596606 2.166087280.022255 1.3148158 0.395289 1.73195975 0.003253 rs440238 0.780607580.249509 0.6858094 0.289683 0.62828413 0.003296 rs1892803 1.614779470.197508 2.047579 0.051301 1.87206666 0.003382 rs4077341 0.689279790.081574 0.5588144 0.09436 0.64621499 0.003529 rs9826296 0.660173370.151245 0.3971541 0.113562 0.52284161 0.003691 rs7348444 0.529391930.023356 0.4970193 0.190505 0.55604255 0.003698 rs4752904 0.760911280.226668 0.5529907 0.124866 0.6347428 0.003793 rs2305340 0.631297790.078361 0.611059 0.231062 0.57482385 0.004047 rs805274 0.652126240.086562 0.6270542 0.250577 0.60927983 0.004506 rs1411479 1.785099690.018214 1.3503939 0.371962 1.54973639 0.004739 rs2076620 2.41970510.017011 1.5093295 0.2763 1.72576938 0.004784 rs4724231 0.337631340.000434 1.5707582 0.455405 0.54856423 0.004812 rs7715375 0.337257740.000385 0.5863538 0.260186 0.57386348 0.004888 rs7289754 0.979441480.925697 1.914168 0.028269 1.51042662 0.005001 rs12310405 0.481127750.002654 0.5978915 0.122106 0.64180759 0.005105 rs3845422 0.570305520.019916 0.8460937 0.658978 0.62448923 0.005195 rs17671456 1.749296370.135263 2.3760572 0.03417 1.84786063 0.005214 rs1885831 0.633438630.092772 0.5213094 0.059969 0.59943237 0.005315 rs4472605 1.44808490.1795 1.6525984 0.290559 1.71977212 0.005454 rs5743740 1.784878270.293217 1.5375034 0.141189 1.64973302 0.005618 rs2070123 0.430088350.003914 0.6554991 0.55009 0.54320594 0.005738 rs2179694 0.928794290.790802 3.368561 0.003379 1.69672289 0.00581 rs6782288 0.397599910.037481 0.4908602 0.565263 0.37100891 0.005937 rs1877563 0.556847040.050965 0.6579718 0.46717 0.53488592 0.00596 rs1781795 1.301288930.435285 3.7963966 0.013791 1.79286631 0.006042 rs9862163 1.348175890.353439 2.1946518 0.033418 1.72813239 0.006094 rs1882019 0.636156240.125724 0.4658273 0.039454 0.57016001 0.006136 rs704853 1.336833460.478197 1.7018946 0.331614 1.89108031 0.006153 rs2278324 2.094612140.033909 0.6946357 0.467913 1.8096482 0.006165 rs10854166 1.66046750.021344 1.7877334 0.033866 1.46340143 0.00628 rs7692976 0.61997140.036045 0.4853325 0.041857 0.66237867 0.006377 rs1046780 0.660196940.070308 0.4180109 0.096451 0.62021487 0.006407 rs7124275 0.659688420.065168 0.4946616 0.047331 0.66309631 0.006437 rs1007212 1.238491850.328324 2.5238917 0.022182 1.51376079 0.006451 rs4498385 0.93594760.842582 2.6856314 0.0044 1.7145818 0.006549 rs3788151 0.459718940.032168 0.4692903 0.191761 0.49784173 0.006566 rs11740298 0.511088390.004835 0.4781692 0.036943 0.64372536 0.006595 rs3815003 0.553976060.015021 0.7295119 0.357161 0.63788244 0.006611 rs6482647 0.729232810.146873 0.366263 0.00172 0.67581779 0.006639 rs2296449 0.48813570.126849 0.2422667 0.037285 0.37611586 0.006711 rs5746154 0.497115680.019558 0.5347065 0.193474 0.57034852 0.00682 rs2020902 1.166034250.61948 3.7147925 0.001012 1.71795081 0.007013 rs927010 0.521077840.006163 0.6631102 0.213678 0.65567615 0.007139 rs5743220 2.670557520.043275 2.5838069 0.003556 1.82790198 0.007171 rs499205 0.867252510.574219 0.6589784 0.142653 0.63787515 0.007211 rs2302267 1.120159330.773011 1.6738235 0.125114 1.63232737 0.007507 rs6214 1.669980210.038224 1.2172621 0.587461 1.52347214 0.007528 rs1105238 1.346819460.232658 2.3356971 0.044995 1.55829502 0.007586 rs12881815 4.971719310.127892 0.1594134 0.227197 3.48147191 0.007641 rs10054825 0.606413770.119365 0.4329791 0.193943 0.52374625 0.00772 rs10836342 1.406905290.14235 2.3160284 0.033397 1.53591151 0.007793 rs3819496 0.570368310.014751 0.7897393 0.37771 0.68159392 0.007819 rs12831813 0.514991150.004238 0.377223 0.030721 0.64167123 0.00783 rs2157605 0.576449260.050925 0.6112004 0.284326 0.60077721 0.007938 rs9487735 3.440899910.044818 1.8293887 0.163324 2.03268322 0.007957 rs9817149 2.517504250.226386 2.8928281 0.211151 2.49550151 0.007992 rs731305 2.123945070.001996 0.8473802 0.633993 1.49787227 0.00801 rs304839 1.195538170.53873 2.0670691 0.028862 1.59400528 0.008054 rs10406354 0.436857070.002456 0.9280367 0.866827 0.60235771 0.008131 rs17763453 1.895669450.043789 0.9999378 0.99985 1.586918 0.008228 rs2569190 1.856767390.008373 0.9048112 0.753205 1.48229265 0.008591 rs6476985 1.995720720.052198 1.4211996 0.440595 1.75826409 0.008892 rs31519 1.341181390.168684 1.2511892 0.47218 1.45400608 0.008925 rs1267843 0.758512770.191668 0.4847643 0.027298 0.68344853 0.008954 rs766502 0.715819850.215636 0.5896612 0.18091 0.60332621 0.009015 rs8064821 1.52729990.22594 1.8307243 0.062525 1.67441451 0.009026 rs4646077 1.315854070.293626 2.4601659 0.013612 1.56944648 0.009194 rs7851161 1.631607410.028346 1.3056665 0.481747 1.48323184 0.009247 rs1983165 0.597527420.04053 0.5354805 0.091546 0.64175505 0.009281 rs10074391 1.819290940.157439 2.4042461 0.024418 1.88111528 0.009311 rs7170919 0.587558280.030705 0.6621434 0.272516 0.64631894 0.009471 rs4251520 0.438074450.002496 0.5157325 0.204856 0.60090009 0.009474 rs1465073 0.789606690.285671 0.562159 0.070661 0.68081974 0.009555 rs613613 0.95785720.851436 0.4848659 0.074112 0.63129647 0.009574 rs2298877 0.564924160.027495 0.7020929 0.315076 0.63080907 0.00968 rs17815972 0.6465250.059999 0.721396 0.362499 0.67719779 0.009696 rs12810163 2.286815380.00231 0.9033077 0.705934 1.4770605 0.009733 rs2267908 1.279037060.312618 1.5601867 0.127776 1.48002659 0.009809 rs7099752 0.677633120.152196 0.4246379 0.014247 0.6251713 0.009934

TABLE 2 SNP Chrom BP Region Gene HGDS Odds HGDS P HIGS Odds rs4147385 5179610123 intron MAPK9 3.06812 0.00017 2.38891621 rs11744216 5 169018841intron DOCK2 0.4561879 0.208945 0.22571238 rs3211834 7 80118053 intronCD36 0.6527446 0.148737 0.5107696 rs1863993 5 169142758 intron DOCK25.8579407 0.007855 1.86996236 SNP HIGS P MIBS Odds MIBS P Meta Odds MetaP rs4147385 0.009361 0.9774443 0.964997 2.34125982 2.64E−05 rs117442160.000282 0.5203063 0.446126 0.29801285 8.24E−05 rs3211834 0.0032510.7359888 0.413646 0.58620393 0.000818 rs1863993 0.560579 4.71309810.033933 4.42496425 0.000876

TABLE 3 SNP Chrom BP Region Gene HGDS Odds HGDS P HIGS Odds rs1236882912 93326073 intron CCDC41 0.37742656 0.3719435 0.23749353 rs11744216 5169018841 intron DOCK2 0.42381549 0.16683371 0.27989213 rs4147385 5179610123 intron MAPK9 2.90585493 0.00015755 2.46419229 rs12546235 823018464 intron TNFRSF10C 0.74208 0.4523308 0.37576137 rs10054825 575837339 intron IQGAP2 0.42794347 0.06709021 0.324665 rs17535213 1242414658 intron PUS7L 1.24887348 0.53836493 0.49318189 rs10072056 5149485499 intron PDGFRB 1.02326444 0.93339826 0.58186139 rs1863993 5169142758 intron DOCK2 5.4206873 0.00889405 1.79012818 rs4242389 823028266 intron TNFRSF10C 1.15216553 0.72881368 0.39817123 rs17725712 5149471001 intron CSF1R 2.22229411 0.10166478 2.97352599 rs11773821 7157648848 intron PTPRN2 0.73075367 0.30225159 0.45675984 rs414634 1589157257 intron BLM 1.9210693 0.01250141 1.76721841 rs1882019 12102861797 intron HSP90B1 0.6021514 0.26821719 0.54596795 rs13206518 66098001 intron F13A1 0.7602344 0.61761633 0.47126387 rs927335 1135207094 intron CD44 1.49735827 0.13592394 1.62199792 rs6482644 10129715311 intron PTPRE 0.63879315 0.09490834 0.76981675 rs4077341 823018293 intron TNFRSF10C 0.65107201 0.11146361 0.63450801 rs1884564 201820658 intron LOC728018 0.8398416 0.63023802 0.45784275 rs3826392 1711863629 locus-region MAP2K4 0.50984063 0.0470141 0.64374497 rs390406 1944920811 locus-region CLC 0.67199333 0.24554649 0.44814554 rs440238 99006071 intron PTPRD 0.3742515 0.00171654 0.70059683 rs9482888 6128855804 intron PTPRK 6.37861557 0.00413766 0.26952546 rs2596606 1875263804 intron NFATC1 1.8666183 0.0500392 2.02654187 rs17652304 575912949 intron IQGAP2 4.57533583 0.00457208 1.64105085 rs3815003 1589113827 intron BLM 0.70729829 0.27605212 0.58889226 rs2278324 538917360 intron OSMR 2.37666019 0.01048799 1.89816183 rs805274 631773173 intron BAT5 0.54648165 0.05304876 0.62947384 rs8005905 14101638120 coding-nonsynonymous HSP90AA1 0.29750544 0.03237554 0.45357526rs2879097 17 34143085 locus-region PCGF2 0.40531332 0.012715780.64069429 rs9313487 5 169394879 intron DOCK2 0.65304879 0.541874850.43957631 rs2227827 5 76054800 intron F2R 1.27420544 0.675633282.20757565 rs246392 5 149477865 intron PDGFRB 1.44908755 0.195291880.56867017 rs6476985 9 5507559 intron PDCD1LG2 1.81397217 0.083892582.17561674 rs7072398 10 6119852 intron IL2RA 0.98642587 0.955662830.57726445 rs1041067 1 158723751 intron SLAMF6 2.22338393 0.008978810.43080195 rs12667537 7 157343101 intron PTPRN2 0.54309148 0.034562220.70517477 rs208250 20 40849159 intron PTPRT 1.26889064 0.345969451.57736681 rs6214 12 101317699 mrna-utr IGF1 1.51571578 0.100176621.61292084 rs10074391 5 149486896 intron PDGFRB 1.3729007 0.494074952.59859713 rs161042 5 146166067 intron PPP2R2B 1.37885068 0.351425760.38138725 rs2071336 16 11969175 coding-synonymous TNFRSF17 1.845763620.23985979 0.10982398 rs6837303 4 111189034 locus-region ELOVL60.58664046 0.06337587 0.69472635 rs3845422 1 179279594 intron MR10.60462117 0.10857967 0.56363662 rs1638006 7 157177926 intron PTPRN20.7297433 0.30670775 0.62866877 rs161021 5 146189300 intron PPP2R2B1.46158082 0.27343607 0.36047838 rs1003854 21 44534535 intron AIRE0.63701493 0.15602551 0.61640983 rs1378796 3 158614482coding-nonsynonymous VEPH1 0.82036206 0.59575804 0.52764493 rs1205176917 11918677 intron MAP2K4 0.53301285 0.06298351 0.64982994 rs3795326 1158732980 intron SLAMF6 1.9796942 0.02997707 0.31717254 rs7170919 1589115963 intron BLM 0.71523388 0.27054948 0.61102113 rs7130876 1148007571 intron PTPRJ 1.36521018 0.29227446 0.52537558 rs244090 2042667504 intron PKIG 1.82658167 0.05072084 1.86114844 rs424051 9 9004740intron PTPRD 0.357172 0.00154964 0.73786157 rs7246376 19 8109328coding-nonsynonymous FBN3 1.41417418 0.2510527 1.68780469 rs12959952 1846494835 intron MAPK4 0.75832189 0.28250053 0.68642326 rs11952962 575931035 intron IQGAP2 1.96820647 0.02211585 1.41785272 rs246394 5149478344 intron PDGFRB 1.15547435 0.61541149 0.63067265 rs12325842 1711935497 intron MAP2K4 0.54254452 0.08441604 0.64627154 rs17763453 173664884 intron C17orf85 1.92846791 0.0172052 1.89696314 rs4472605 934556190 intron CNTFR 2.29595354 0.01632828 1.45596316 rs926479 2040786436 intron PTPRT 1.25796536 0.71984049 2.59667403 rs2071081 126805892 locus-region LEPREL2 1.16018832 0.62051063 1.72458275 rs76903054 15575064 — — 0.6947075 0.28024405 0.57017516 rs244076 20 42686329coding-synonymous ADA 1.79952848 0.05747238 1.8756407 rs6621980 23104690227 intron IL1RAPL2 1.20558533 0.30138287 1.3068943 rs6742576 2239852569 intron HDAC4 2.04564913 0.04916586 1.55889951 rs866484 1157253101 coding-nonsynonymous IFI16 1.34340774 0.32362484 1.56924172rs3797390 5 75942821 intron IQGAP2 2.35975324 0.00250135 1.20099738rs1264456 6 30570063 — — 0.60087672 0.05481569 0.6298167 rs6065467 2040432747 intron PTPRT 0.66417197 0.30045815 0.56971475 rs3736395 575924224 intron IQGAP2 2.01317446 0.01786271 1.38697287 rs9892152 1759755697 intron PECAM1 1.28015545 0.30060169 1.79832413 rs4955104 330696707 intron TGFBR2 1.73311846 0.09135101 1.70995826 rs1007212 1597101441 intron IGF1R 1.58554575 0.06881669 1.27530638 rs2296449 1117380273 intron IGSF2 0.28435755 0.2386029 0.47588685 rs832517 1293164318 intron PLXNC1 0.73260276 0.2419302 0.68112858 rs5743220 1143299463 intron API5 0.82693415 0.64066747 2.44655616 rs8086815 188163669 intron PTPRM 1.13288097 0.73780601 1.6337126 rs3733678 5149491985 intron PDGFRB 1.56157271 0.31028198 2.06780589 rs246395 5149479865 coding-synonymous PDGFRB 1.43776518 0.19768884 0.6194716rs613613 9 9004274 intron PTPRD 0.24492626 0.00030665 0.83677802rs10406354 19 59022044 — — 0.84350808 0.63607216 0.52404025 rs1105238 1159948285 intron FCRLA 1.57425902 0.08700505 1.35815008 rs4724231 743608739 intron STK17A 0.79408653 0.52206122 0.37564254 rs2179694 6128405416 intron PTPRK 2.72734178 0.00371434 1.10418786 rs210431 23104831589 intron IL1RAPL2 1.15706404 0.41697392 1.25792622 rs17671456 822441022 intron PPP3CC 1.62279091 0.18971454 1.60308204 rs17283264 346228570 — — 1.71885877 0.13929326 6.6280982 rs2279590 8 27512170 intronCLU 0.88843705 0.64964423 1.75040285 rs1050382 17 59753732 locus-regionPECAM1 1.28401592 0.30420932 1.74401131 rs6917187 6 128870789 intronPTPRK 1.30160689 0.56966629 0.46217996 rs933226 22 30673847 intron YWHAH1.12742146 0.73874752 1.98104948 rs3024486 6 6090408 mrna-utr F13A11.88372078 0.23198551 8.87599881 rs4698806 4 111190938 mrna-utr ELOVL60.57535324 0.05772595 0.75961836 rs4756331 11 36602169 intron C11orf744.6856564 0.03167379 2.27441112 rs10772120 12 9801678 intron CD690.65812083 0.15886236 0.65374546 rs4820059 22 30676468 intron YWHAH0.89142053 0.67014566 1.72048152 rs7099752 10 129641321 intron PTPRE0.81583787 0.56389734 0.6887796 rs10797666 1 179285422 intron MR10.6992695 0.22630081 0.58684061 rs831603 11 33715214 — — 0.735862140.24049237 0.69047971 rs1519602 2 196736037 intron STK17B 0.571787090.03485524 0.73904041 rs638251 18 7786393 intron PTPRM 0.922672060.75903463 0.60830628 rs7541717 1 71179181 intron PTGER3 0.773361480.38262508 0.55588639 rs793816 4 185591486 intron IRF2 0.392686270.40453998 0.23730079 rs805287 6 31786709 locus-region C6orf210.57505168 0.05667066 0.69044701 rs2844463 6 31723146 intron BAT30.37152482 0.02080519 0.7124517 rs11237451 11 77703107 intron GAB20.6976664 0.24743993 0.73454025 rs496888 1 12155393 intron TNFRSF1B0.98980954 0.97027764 0.58209238 rs2163057 3 32514492 intron CMTM60.67697442 0.14595214 0.70525773 rs2283539 16 24036462 intron PRKCB11.34410531 0.26558516 1.67553526 rs4253655 22 44947835 intron PPARA1.91645477 0.04617801 1.54643399 rs1075846 5 149484351 intron PDGFRB0.98153804 0.94437916 0.6804459 rs10836342 11 35198213 intron CD441.39906967 0.22563757 1.55571501 rs17419586 13 23148712 locus-regionTNFRSF19 1.0920234 0.74357188 1.8778521 rs2076846 10 6103259 intronIL2RA 1.01897585 0.94283005 0.59088718 rs17110948 5 149498698 intronPDGFRB 0.75555493 0.58881604 0.49768788 rs7289754 22 20926259 — —2.29698009 0.00141594 1.08058008 rs3736101 11 47263204coding-nonsynonymous MADD 1.97297758 0.05712124 2.67813862 rs10807350 647336871 intron TNFRSF21 0.90243854 0.76800828 2.03966167 rs2575674 487156570 locus-region MAPK10 1.06794408 0.82242424 0.58503629 rs14365224 87183196 intron MAPK10 0.81807545 0.56253571 0.61156718 rs2869460 477140838 locus-region CXCL9 0.70455921 0.3038615 0.58827213 rs1288181514 63674348 coding-nonsynonymous SYNE2 4.89460691 0.00447504 3.27810424rs2302267 23 12795499 intron TLR7 1.92239964 0.0134585 1.4130263rs4966019 15 97091849 intron IGF1R 1.67417263 0.03214425 1.21425194rs6482647 10 129716363 intron PTPRE 0.89887749 0.66494004 0.74977347rs4027402 14 63566502 coding-nonsynonymous SYNE2 0.39821095 0.030352310.76414481 rs10789841 11 110974792 — — 1.53893299 0.09589358 0.47137687rs1983165 3 62059196 intron PTPRG 0.76500869 0.39230788 0.6522553rs6670616 1 71167471 intron PTGER3 0.74220682 0.31748959 0.58708357rs896769 7 157770740 intron PTPRN2 0.49460614 0.35898709 0.43950595rs1984399 20 40312545 intron PTPRT 1.35296357 0.22045301 1.46992979rs4955272 3 32288680 intron CMTM8 0.92003691 0.78923423 0.60948044rs2869461 4 77139917 locus-region CXCL9 1.26643088 0.53864183 1.85274565rs2286414 7 157167781 intron PTPRN2 2.49603643 0.05177127 3.78156695rs878081 21 44532705 coding-synonymous AIRE 0.68171151 0.227022260.66315301 rs791587 10 6128705 intron IL2RA 0.84136254 0.48151920.64120998 rs4902264 14 63561448 coding-nonsynonymous SYNE2 0.416336940.03348373 1.91932441 rs13172280 5 35063668 intron AGXT2 1.306566330.28540035 1.73502557 rs2569190 5 139993100 intron CD14 1.507560380.1077863 1.59274474 rs660597 5 131422350 locus-region IL3 1.302211560.69582292 0.42665893 rs6016685 20 40173215 intron PTPRT 0.929518720.79976593 0.59082396 rs6060855 20 29762606 intron BCL2L1 1.043950.92304559 0.43117643 rs4752896 11 48086525 intron PTPRJ 3.727086360.00528618 1.57506212 rs244091 20 42664524 intron PKIG 1.946534930.04751127 1.75887237 rs2070783 17 59760703 intron PECAM1 1.237344920.37520045 1.75467319 rs169142 16 24039431 intron PRKCB1 0.679015270.10717015 0.71324157 rs2335478 7 157569741 intron PTPRN2 1.581886870.42862493 0.39743275 rs10514071 5 76029967 intron IQGAP2 1.659413840.07707822 1.2178954 rs3828016 20 1865290 intron SIRPA 0.528525230.02160896 0.70944458 rs1457238 2 160693708 intron ITGB6 0.970201260.91163481 0.72059793 rs11015985 10 129669308 intron PTPRE 0.940834930.84162285 0.67420508 rs12001295 9 5508260 intron PDCD1LG2 1.792439040.2162097 1.95909625 rs2267908 20 1857920 intron SIRPA 1.681712210.04729491 1.23185694 rs12625871 20 40208063 intron PTPRT 0.688421840.47143938 0.51747943 rs1058240 10 8156604 mrna-utr GATA3 0.75659520.4352407 0.60486059 rs9310940 3 30697222 intron TGFBR2 1.749834490.02369938 1.26424017 rs12814009 12 15399298 intron PTPRO 0.263565740.01629732 0.64133422 rs7559522 2 45903540 intron PRKCE 1.012493620.95884972 0.65154256 rs1797647 12 12143345 mrna-utr BCL2L14 0.678920260.1815313 0.74897192 rs304839 3 30706286 intron TGFBR2 1.709276670.0746808 1.27375763 rs10972149 9 34551160 intron CNTFR 1.881317240.06984944 1.40551155 rs2069933 2 127902158 intron PROC 1.53223740.08604038 1.41197006 rs12969613 18 65710412 intron CD226 0.910362510.7111396 0.73759216 rs2275603 1 159948404 coding-nonsynonymous FCRLA1.4835256 0.13666372 1.33588972 rs1044141 7 43630805coding-nonsynonymous STK17A 1.37913032 0.28521545 1.54280229 rs100782218 65706201 intron CD226 0.91036251 0.7111396 0.73861498 rs7692976 4111131016 intron EGF 0.83961089 0.48533216 0.72312756 rs4485556 2219865662 intron PTPRN 1.09221296 0.78285734 2.06334949 rs2231375 1144408051 intron CD160 0.74115317 0.2635782 0.69538709 rs2242660 631705732 intron BAT2 0.76945122 0.35472586 0.63732275 rs7732671 5149192436 coding-nonsynonymous PPARGC1B 2.89131579 0.00898077 1.55843339rs17834679 19 56961899 intron FPRL1 0.59646363 0.07510676 0.67581905rs2838733 21 45148159 intron ITGB2 1.41619634 0.20650687 1.4139189rs13173943 5 35037762 intron AGXT2 1.41575487 0.17774415 1.76018633rs4462251 10 129749982 intron PTPRE 0.71790728 0.18078977 0.6649517rs2305340 12 7157242 — — 0.42720319 0.03847928 0.73801084 rs12451415 1711947505 intron MAP2K4 0.38601795 0.01940391 0.74534892 rs2595204 246047369 intron PRKCE 1.04828765 0.8648604 1.57921594 rs6021183 2049455556 intron NFATC2 1.27572604 0.48092282 2.90323676 rs17113227 11111125701 intron PPP2R1B 1.31079147 0.28991073 4.48E−73 rs11833550 129899947 intron CLEC2B 1.43123546 0.28432538 1.47738548 rs310247 165079997 intron JAK1 1.49052622 0.12938444 1.44027852 rs17875513 1579379439 coding-nonsynonymous IL16 2.09E−10 0.99976301 0.10166663rs910682 6 112282428 intron FYN 2.12093972 0.0119868 Inf rs4245886 332279107 intron CMTM8 0.7970233 0.41988177 0.73876461 rs12185980 3107031592 intron CBLB 3.323853 0.00050792 1.56530554 rs2255364 1210423163 intron KLRK1 0.5616856 0.08521285 1.56368161 rs2268890 2162580738 intron DPP4 0.65149321 0.09885744 1.20E+25 rs6058391 2029743569 intron BCL2L1 1.11886253 0.80671459 0.44238887 rs7647903 33108791 intron IL5RA 1.87725168 0.02334544 1.23815585 rs5996577 2222251427 intron IGLL1 1.92827739 0.037121 1.72345433 rs6580942 1251948891 coding-nonsynonymous ESPL1 1.18080511 0.54440371 1.46959364rs241430 6 32910798 intron TAP2 0.53117149 0.02212076 1.69161859rs706121 9 33250632 intron BAG1 0.86147211 0.63269212 2.22530992rs2295616 1 158976781 intron SLAMF7 0.82924496 0.49284778 0.58465681rs6829390 4 47893743 intron TEC 1.7333281 0.14893786 3.03190369rs9817149 3 191740949 intron IL1RAP 2.32356443 0.05341758 1.86248097rs599563 1 117014117 — — 0.52790505 0.12915023 0.20622181 rs2238337 1589156736 intron BLM 1.54569338 0.08136811 1.50742576 rs3816724 1147268621 intron MADD 1.81113639 0.10869127 2.65901484 rs970283 2040713729 intron PTPRT 1.46306145 0.4018486 0.54068963 rs3733236 477143022 mrna-utr CXCL9 1.15699539 0.71638395 1.83954612 rs10854166 1918513844 intron FKBP8 1.03811743 0.87944921 1.47150955 rs6850557 4111130464 intron EGF 1.19374349 0.51028325 0.61087182 rs4572808 332292718 intron CMTM8 1.1777916 0.53590471 1.32095634 rs875258 11111035817 intron SNF1LK2 1.21639487 0.45485149 Inf rs1131510 10 35339091mrna-utr CUL2 1.04488097 0.93034401 0.32944623 rs10497208 2 160695167intron ITGB6 0.97020126 0.91163481 0.73334585 rs10104302 8 57030794intron LYN 1.23920621 0.4864228 1.44246121 rs728373 20 40278187 intronPTPRT 1.35050667 0.2291808 1.37699658 rs10977434 9 8991075 intron PTPRD1.26538151 0.35953996 1.59504212 rs12039194 1 162803852 intron PBX10.91594261 0.82318503 0.52789908 rs2853884 22 30678313 intron YWHAH1.0223608 0.93977544 1.49159144 rs5743740 23 12801881 intron TLR71.71683397 0.03335376 1.53079545 rs7359387 16 68291166 mrna-utr NFAT50.72860948 0.42312929 0.5709194 SNP HIGS P MIBS Odds MIBS P Meta OddsMeta P rs12368829 1.55E−07 1.887207952 0.56468936 0.27311013 5.08E−07rs11744216 1.44E−05 0.370067427 0.28008697 0.30667899 3.56E−06 rs41473850.00046696 0.847419164 0.67342809 2.13745578 9.22E−06 rs125462359.63E−06 0.258959962 0.19881566 0.43388002 1.11E−05 rs10054825 0.00018970.514031922 0.25064205 0.3743547 2.21E−05 rs17535213 4.45E−060.588339124 0.31166083 0.57027044 4.02E−05 rs10072056 0.000742270.414680192 0.0012715 0.60837768 5.84E−05 rs1863993 0.443191574.427219418 0.00214385 3.88981038 8.36E−05 rs4242389 8.81E−060.538507051 0.52261252 0.49632251 0.00011364 rs17725712 0.011955222.373592311 0.01979588 2.50759989 0.00016535 rs11773821 0.00084520.518178068 0.13897121 0.54041127 0.00033105 rs414634 0.001771280.981460036 0.95270754 1.62246205 0.00033946 rs1882019 0.005752730.47389969 0.04123021 0.53629298 0.00034044 rs13206518 0.029305690.117803784 0.00019143 0.39427174 0.00035099 rs927335 0.014108752.78864964 0.01285391 1.69891458 0.00036195 rs6482644 0.247688470.247282655 6.13E−05 0.57798945 0.00040403 rs4077341 0.005192010.608350511 0.14814984 0.63448794 0.00042665 rs1884564 0.000162320.787331851 0.64569651 0.55434198 0.00051894 rs3826392 0.00846760.693166599 0.2022867 0.6309839 0.00053597 rs390406 0.000114951.176428114 0.70671054 0.56597223 0.00053686 rs440238 0.041955410.703829319 0.29007635 0.62008121 0.00057369 rs9482888 NA 6.8194909380.05718065 6.50375409 0.00058077 rs2596606 0.00317447 1.2881869480.42621042 1.75806233 0.00058124 rs17652304 0.49335132 4.8919794430.0296099 3.55426184 0.00062941 rs3815003 0.00175443 0.7059675040.29860931 0.62769907 0.00064177 rs2278324 0.00282462 0.6659509880.42252987 1.78495491 0.00068524 rs805274 0.01306354 0.6094047920.18569727 0.60696173 0.0006948 rs8005905 0.0003978 1.4147062740.44027301 0.52877353 0.00072601 rs2879097 0.00665552 0.8852002630.72785514 0.63044699 0.00079205 rs9313487 0.0034416 0.233662250.08429415 0.43740777 0.0008986 rs2227827 0.26149332 5.689435270.00020765 2.92049655 0.00092929 rs246392 0.00056846 0.4593355210.00673323 0.6561279 0.0009419 rs6476985 0.00536715 1.4456697540.41300509 1.89994931 0.00102191 rs7072398 0.00039605 0.6884872850.2008706 0.6750759 0.00102242 rs1041067 NA 2.060320517 0.047796452.15467293 0.00106064 rs12667537 0.02875229 0.597491768 0.143223940.65395062 0.00107733 rs208250 0.00614501 1.840718802 0.076400461.52317417 0.00109109 rs6214 0.0038546 1.188058954 0.61245743 1.519874440.00109655 rs10074391 0.01865724 2.594822575 0.01436067 2.187710540.00112369 rs161042 2.05E−05 0.652465532 0.233342 0.58028375 0.00114124rs2071336 5.19E−07 0.428886818 0.29502796 0.36521665 0.00117968rs6837303 0.03179239 0.572171902 0.09253608 0.6489751 0.00122167rs3845422 0.00278781 0.888862119 0.7473235 0.61787249 0.00126245rs1638006 0.00560578 0.606535032 0.17368201 0.64416528 0.00128998rs161021 7.72E−06 0.708220637 0.35425816 0.57994142 0.00131834 rs10038540.00808487 0.658007833 0.25304841 0.62708448 0.00132688 rs13787960.00049546 0.883688589 0.74236331 0.6161596 0.00132949 rs120517690.00843671 0.794312841 0.45113646 0.65464663 0.00141068 rs3795326 NA2.279926623 0.01881296 2.10832635 0.00145114 rs7170919 0.005473740.654104992 0.24394214 0.63862525 0.00149694 rs7130876 0.000268770.369125944 0.02598111 0.63472671 0.00155036 rs244090 0.009181381.243594423 0.53464137 1.69120653 0.00156555 rs424051 0.083789240.718400103 0.35041277 0.64014939 0.00164957 rs7246376 0.015775552.427149459 0.0560574 1.67623062 0.00170637 rs12959952 0.053076490.446458552 0.00878972 0.64752915 0.00171155 rs11952962 0.141023052.023094389 0.0652907 1.68301113 0.00177679 rs246394 0.004528910.449778283 0.00878434 0.67006344 0.00180216 rs12325842 0.010573380.770807589 0.41269576 0.65064375 0.00190847 rs17763453 0.010339021.010710537 0.97540609 1.65815902 0.00193618 rs4472605 0.055292581.745523547 0.23595804 1.6397061 0.00203956 rs926479 0.073535947.99520442 0.00126005 2.90414967 0.00204443 rs2071081 0.017715131.911456413 0.0218428 1.60296551 0.00207988 rs7690305 0.002906210.824326571 0.64212974 0.62430077 0.00208977 rs244076 0.010074641.204884408 0.59491143 1.6732152 0.00221531 rs6621980 0.049399861.775653247 0.01210697 1.35035351 0.00223866 rs6742576 0.063455161.768951867 0.12128795 1.7093299 0.00227372 rs866484 0.063744322.22598424 0.01233101 1.64048747 0.00231235 rs3797390 0.350329611.689002991 0.07241573 1.53728435 0.00232497 rs1264456 0.002456951.465610843 0.3087658 0.6842054 0.00235738 rs6065467 0.001627511.332110088 0.60420493 0.6243462 0.00254874 rs3736395 0.176461021.931419031 0.09472133 1.66559675 0.0025506 rs9892152 0.000762931.035878616 0.89700987 1.45816281 0.00256015 rs4955104 0.011590831.267402965 0.47637974 1.60475149 0.00258158 rs1007212 0.167268642.270349904 0.01221697 1.4869906 0.00269972 rs2296449 0.053034570.252264495 0.03143414 0.39039884 0.00278836 rs832517 0.017336390.641773703 0.15867567 0.68581238 0.00283581 rs5743220 0.007549932.215631346 0.01089829 1.81228752 0.00284212 rs8086815 0.049667265.059080213 0.00088215 1.76520819 0.00293494 rs3733678 0.029962962.076872691 0.06617482 1.92823675 0.00300019 rs246395 0.002367940.46651283 0.00816981 0.69198318 0.00301278 rs613613 0.338519240.489338494 0.06231333 0.63373233 0.00303403 rs10406354 0.001212810.862175398 0.72870567 0.6194692 0.00304803 rs1105238 0.101636622.428288153 0.02817001 1.52456935 0.00317617 rs4724231 0.000203241.552093052 0.46472493 0.55470559 0.00329302 rs2179694 0.647708792.925008861 0.00555316 1.6268167 0.0033713 rs210431 0.069914521.942062547 0.0046256 1.31935745 0.00342114 rs17671456 0.066297752.201374994 0.04659244 1.72457302 0.00342623 rs17283264 0.001486291.526652324 0.53071016 2.2848273 0.00352712 rs2279590 0.001063841.676816197 0.11287341 1.46446386 0.00357173 rs1050382 0.001679561.062141736 0.83590345 1.45390139 0.00357423 rs6917187 9.24E−052.057353645 0.23760335 0.60379164 0.00375548 rs933226 0.013374942.189801618 0.04098616 1.73409156 0.00381266 rs3024486 0.017281172.856438354 0.06567196 2.80749677 0.00387647 rs4698806 0.110309640.527501004 0.06278053 0.67517857 0.00390396 rs4756331 0.171902882.903606511 0.11955976 3.01226743 0.00395009 rs10772120 0.011689650.821815393 0.59634724 0.6752583 0.00397005 rs4820059 0.002872571.914602607 0.04428658 1.48141208 0.00404405 rs7099752 0.059565650.404212531 0.00954005 0.64097952 0.00405109 rs10797666 0.003300480.991516881 0.98022829 0.667058 0.00408808 rs831603 0.030757350.584849703 0.11700827 0.6846441 0.00416496 rs1519602 0.082363040.674616309 0.24306781 0.68252708 0.00424479 rs638251 0.001360030.86397335 0.61888292 0.70643279 0.00426573 rs7541717 0.002694270.907922766 0.81093925 0.64956179 0.00430369 rs793816 0.0057848818864431544 NA 0.25951327 0.00431797 rs805287 0.0476095 0.7120275430.34602151 0.66328443 0.0043842 rs2844463 0.08520158 0.5071723130.16989179 0.61948187 0.00443233 rs11237451 0.06356768 0.386396990.01979918 0.67561604 0.00449866 rs496888 0.00079136 0.8696515380.64305507 0.69866146 0.00451876 rs2163057 0.03329755 0.7306652140.22869821 0.70474573 0.00454599 rs2283539 0.01026196 1.332566740.35974288 1.49931704 0.00454803 rs4253655 0.0722436 1.5877431470.29093345 1.65541438 0.00459501 rs1075846 0.01175816 0.5983918020.05711767 0.71375152 0.00461622 rs10836342 0.06567563 2.1032853370.04913566 1.58639988 0.00478853 rs17419586 0.00291577 1.5467435960.22555031 1.52993899 0.00486913 rs2076846 0.00126669 0.7644928660.4048416 0.69945436 0.00498422 rs17110948 0.01809374 0.431355050.10282208 0.52503672 0.00502749 rs7289754 0.67991022 1.7143545140.06533309 1.46058131 0.00505693 rs3736101 0.01446908 1.1785602990.71300002 1.90168302 0.0050709 rs10807350 0.02125369 4.201064860.00152376 1.78016031 0.00510485 rs2575674 0.00106201 0.7926786850.4959151 0.69155684 0.00515029 rs1436522 0.00435674 0.8306573960.6115842 0.67275763 0.00532612 rs2869460 0.0026252 1.0910404470.80696993 0.67117457 0.00542323 rs12881815 0.07772938 0.1800403810.20551442 3.11823429 0.00551016 rs2302267 0.30851561 1.4268217750.25585508 1.61823347 0.00555203 rs4966019 0.26208827 2.2180146170.03331489 1.43993702 0.0055734 rs6482647 0.06781404 0.3855149160.003037 0.71192776 0.0056319 rs4027402 NA 0.417903186 0.084556220.4062491 0.00564909 rs10789841 NA 1.857069082 0.02350067 1.681985150.00566318 rs1983165 0.03014415 0.549314197 0.10127566 0.657397320.00570624 rs6670616 0.00682232 0.838342811 0.65037355 0.658176960.00571641 rs896769 0.00736724 0.753842335 0.64705164 0.489716260.00577494 rs1984399 0.0342318 1.525981289 0.1905506 1.443934910.00587133 rs4955272 0.00517256 0.718705374 0.30795068 0.68192440.00590934 rs2869461 0.01548032 1.861727809 0.14918366 1.688966220.00591907 rs2286414 0.05552253 2.007269628 0.50111889 2.723990910.00597573 rs878081 0.0286662 0.695807839 0.25365564 0.6735551 0.0060638rs791587 0.01422135 0.688406679 0.18017542 0.70198049 0.00615988rs4902264 NA 0.417903186 0.08455622 0.41696109 0.00618391 rs131722800.0036724 1.039486719 0.90369822 1.45208431 0.00635965 rs25691900.00646771 0.880141582 0.69107942 1.42512534 0.00638771 rs6605970.00578686 0.138854042 0.06951693 0.4765705 0.00640015 rs60166850.00271653 0.791056985 0.56022757 0.68182883 0.00640311 rs60608550.00181195 0.66791201 0.40088926 0.56756344 0.0064531 rs47528960.16126432 1.391028202 0.48894885 1.88703405 0.00645468 rs2440910.0259514 1.101451332 0.78546353 1.61216431 0.00660832 rs20707830.00171067 1.016006939 0.95267953 1.40916934 0.00673216 rs1691420.0696807 0.698087802 0.22388372 0.69977491 0.00674726 rs23354780.00244836 0.374723896 0.13478287 0.50898606 0.00676621 rs105140710.39124357 2.669520125 0.00978668 1.55132811 0.00677526 rs38280160.04488799 0.931914458 0.80457051 0.70395066 0.00680458 rs14572380.03083353 0.448765762 0.01536078 0.71699591 0.00686438 rs110159850.03157349 0.443734676 0.02237032 0.67800361 0.00687617 rs120012950.05272256 2.21810303 0.1478398 1.96037745 0.00693366 rs22679080.20262375 1.672388773 0.07377876 1.40092131 0.00700235 rs126258710.01079712 0.56080892 0.48307066 0.54867028 0.00702961 rs10582400.0255244 0.501587784 0.13892818 0.62184082 0.00705888 rs93109400.21046792 1.534801231 0.19126356 1.44173233 0.00708699 rs128140090.04018572 0.85737766 0.74635877 0.60684251 0.00714929 rs75595220.00878969 0.653199774 0.09010336 0.72623812 0.00723028 rs17976470.09192002 0.531576091 0.06534918 0.69479558 0.00723465 rs3048390.27377029 1.933369668 0.04096021 1.519783 0.00727028 rs109721490.09827821 1.982803974 0.16022376 1.56393114 0.00727045 rs20699330.07395592 1.400276986 0.28599342 1.4453417 0.00729683 rs129696130.05884827 0.498166411 0.01389573 0.7198681 0.00733444 rs22756030.12468672 2.276509243 0.04563816 1.47070868 0.00737309 rs10441410.05186795 1.73278306 0.11349463 1.53200877 0.00737979 rs10078220.05919215 0.498166411 0.01389573 0.72051256 0.00738553 rs76929760.05480184 0.494195549 0.03069494 0.70892031 0.00749125 rs44855560.00235261 1.397902115 0.50367932 1.61122769 0.00753766 rs22313750.04220739 0.668067207 0.1778523 0.7008452 0.00761801 rs22426600.0150168 0.756806298 0.38886309 0.68903243 0.00770852 rs77326710.11260985 1.154819688 0.78346793 1.75337264 0.00774675 rs178346790.02521038 0.916733777 0.76653341 0.70125031 0.00782735 rs28387330.07614029 1.653502779 0.11273327 1.45987018 0.00786753 rs131739430.00484349 0.945514666 0.86077528 1.45770814 0.00791673 rs44622510.01518388 0.889299251 0.66882685 0.71937813 0.00791696 rs23053400.12689838 0.581977508 0.16118037 0.64965334 0.0079501 rs124514150.12088012 0.678411195 0.25039759 0.66611984 0.00796339 rs25952040.00863162 1.533849353 0.18832877 1.42736818 0.00801759 rs60211830.0045594 1.665236661 0.2895987 1.81521342 0.00802275 rs17113227 NA2.030897722 0.00673784 1.62365628 0.00802282 rs11833550 0.107811542.048397433 0.0466996 1.57886187 0.00812332 rs310247 0.058440841.533403149 0.30009436 1.46685181 0.00847391 rs17875513 0.001946264.488678953 0.44414345 0.16253264 0.00851961 rs910682 NA 1.537262060.32267559 1.91249249 0.0085282 rs4245886 0.05011435 0.6312695580.09390401 0.72659446 0.00855999 rs12185980 0.13376119 0.7434685650.46740879 1.68164239 0.00856073 rs2255364 0.06357989 3.6751775973.23E−05 1.54643136 0.00860527 rs2268890 NA 0.626627758 0.042087160.63743958 0.008899 rs6058391 0.00238366 0.66791201 0.400889260.57929283 0.00891021 rs7647903 0.28448998 2.887094074 0.06366081.50351852 0.00891595 rs5996577 0.02398456 0.590279616 0.359823471.60794968 0.00894574 rs6580942 0.05457562 1.982043892 0.040628731.4624003 0.00903024 rs241430 NA 0.674243811 0.16566189 0.5964530.00913438 rs706121 0.00133522 1.614843189 0.16429715 1.555742680.00914737 rs2295616 0.01231339 0.714667913 0.29309131 0.677936930.00915385 rs6829390 0.00857334 0.850565336 0.8404433 2.004047030.00917152 rs9817149 0.15450723 2.698708717 0.266516 2.139000590.00917463 rs599563 NA 0.346839408 0.02656012 0.43929499 0.00918559rs2238337 0.01187583 0.812838175 0.53897147 1.39071444 0.00918659rs3816724 0.01510082 1.178560299 0.71300002 1.83253888 0.00921881rs970283 0.00445051 0.165726534 0.03992744 0.60917368 0.0092717rs3733236 0.06042245 2.795477626 0.02145048 1.77125565 0.00929059rs10854166 0.03416572 1.756625912 0.03368719 1.3955462 0.00940624rs6850557 0.00404606 0.591937798 0.08975996 0.71197963 0.00948749rs4572808 0.0529861 1.667940453 0.06254176 1.34643121 0.00956242rs875258 NA 2.171635923 0.00343425 1.62007531 0.00963046 rs1131510 NA0.283691506 0.00092772 0.45633087 0.00968206 rs10497208 0.040981830.451737257 0.01743008 0.7270181 0.00969018 rs10104302 0.047265181.968171333 0.07587968 1.45910911 0.00980005 rs728373 0.064625281.569525638 0.16079534 1.39945812 0.00980031 rs10977434 0.013230861.235721111 0.49790003 1.42266906 0.00987629 rs12039194 0.010629060.49832587 0.20360196 0.60172257 0.0098777 rs2853884 0.029668851.927931615 0.04179488 1.43572943 0.00989768 rs5743740 0.228982741.336018859 0.28954961 1.52907649 0.00994335 rs7359387 0.010477560.840613031 0.72747093 0.6307871 0.00995871

TABLE 4 SNP Chrom BP Region Gene HGDS Odds HGDS P HIGS Odds rs1236882912 93326073 intron CCDC41 0.40594217 0.41620935 0.23749353 rs4147385 5179610123 intron MAPK9 3.04945702 0.00017896 2.46419229 rs11744216 5169018841 intron DOCK2 0.44998628 0.20079861 0.27989213 rs17535213 1242414658 intron PUS7L 1.18874097 0.65886311 0.49318189 rs10072056 5149485499 intron PDGFRB 0.9326251 0.81037828 0.58186139 rs10054825 575837339 intron IQGAP2 0.43711187 0.0778727 0.324665 rs12546235 823018464 intron TNFRSF10C 0.72515962 0.4427109 0.37576137 rs2071336 1611969175 coding-synonymous TNFRSF17 1.33642895 0.61691603 0.10982398rs414634 15 89157257 intron BLM 2.2016114 0.00536501 1.76721841rs17725712 5 149471001 intron CSF1R 2.69330968 0.06546239 2.97352599rs4242389 8 23028266 intron TNFRSF10C 1.13500187 0.77037148 0.39817123rs11773821 7 157648848 intron PTPRN2 0.65518824 0.19868332 0.45675984rs8005905 14 101638120 coding-nonsynonymous HSP90AA1 0.348593640.06727143 0.45357526 rs1863993 5 169142758 intron DOCK2 6.339943620.00606025 1.79012818 rs9482888 6 128855804 intron PTPRK 12.57421580.00292392 0.26952546 rs6476985 9 5507559 intron PDCD1LG2 2.003571170.06524366 2.17561674 rs440238 9 9006071 intron PTPRD 0.265044790.00016935 0.70059683 rs2278324 5 38917360 intron OSMR 2.635375330.00743666 1.89816183 rs3826392 17 11863629 locus-region MAP2K40.51063591 0.05983922 0.64374497 rs12051769 17 11918677 intron MAP2K40.46994899 0.03942236 0.64982994 rs1378796 3 158614482coding-nonsynonymous VEPH1 0.75236304 0.47587027 0.52764493 rs6065467 2040432747 intron PTPRT 0.50610715 0.12933303 0.56971475 rs3845422 1179279594 intron MR1 0.58149946 0.10161841 0.56363662 rs208250 2040849159 intron PTPRT 1.27519572 0.3576712 1.57736681 rs1884564 201820658 intron LOC728018 0.78345665 0.52653486 0.45784275 rs424051 99004740 intron PTPRD 0.25267033 0.00014826 0.73786157 rs2596606 1875263804 intron NFATC1 2.41198802 0.00952767 2.02654187 rs9892152 1759755697 intron PECAM1 1.21176807 0.43963293 1.79832413 rs12325842 1711935497 intron MAP2K4 0.46723502 0.0493405 0.64627154 rs3815003 1589113827 intron BLM 0.64453883 0.20681329 0.58889226 rs390406 1944920811 locus-region CLC 0.70248295 0.30742213 0.44814554 rs244090 2042667504 intron PKIG 1.71556712 0.09647363 1.86114844 rs1882019 12102861797 intron HSP90B1 0.65623976 0.36715836 0.54596795 rs2869460 477140838 locus-region CXCL9 0.5058031 0.08717965 0.58827213 rs2879097 1734143085 locus-region PCGF2 0.42515295 0.02198811 0.64069429 rs244076 2042686329 coding-synonymous ADA 1.69508583 0.10765184 1.8756407 rs63825118 7786393 intron PTPRM 0.86837964 0.60834621 0.60830628 rs11952962 575931035 intron IQGAP2 2.19383552 0.01353614 1.41785272 rs10074391 5149486896 intron PDGFRB 1.49513964 0.40643508 2.59859713 rs7170919 1589115963 intron BLM 0.60343656 0.13274345 0.61102113 rs11780679 879821131 intron IL7 0.28969938 0.09898674 0.53730499 rs4077341 823018293 intron TNFRSF10C 0.76205039 0.33129864 0.63450801 rs12001295 95508260 intron PDCD1LG2 2.23381373 0.12694632 1.95909625 rs1003854 2144534535 intron AIRE 0.67130473 0.23146056 0.61640983 rs246392 5149477865 intron PDGFRB 1.38464673 0.28154335 0.56867017 rs7690305 415575064 — — 0.67630525 0.27238321 0.57017516 rs17652304 5 75912949intron IQGAP2 6.53946184 0.0017172 1.64105085 rs9313487 5 169394879intron DOCK2 0.64895553 0.54042356 0.43957631 rs1457238 2 160693708intron ITGB6 1.09178513 0.75352212 0.72059793 rs12692566 2 160384673coding-nonsynonymous LY75 1.77178098 0.0875946 2.19460251 rs3797390 575942821 intron IQGAP2 2.57357265 0.00174144 1.20099738 rs2070783 1759760703 intron PECAM1 1.16581079 0.54097307 1.75467319 rs1264456 630570063 — — 0.6311328 0.09292498 0.6298167 rs1075846 5 149484351 intronPDGFRB 0.84122055 0.54316742 0.6804459 rs6093584 20 40237760 intronPTPRT 0.51129422 0.0273209 0.75714002 rs13173943 5 35037762 intron AGXT21.53186639 0.11764271 1.76018633 rs10797666 1 179285422 intron MR10.67279722 0.2032679 0.58684061 rs4724231 7 43608739 intron STK17A0.88797357 0.74583064 0.37564254 rs613613 9 9004274 intron PTPRD0.1428006 2.54E−05 0.83677802 rs6742576 2 239852569 intron HDAC42.18359035 0.0518853 1.55889951 rs927335 11 35207094 intron CD441.47588642 0.17083319 1.62199792 rs1638006 7 157177926 intron PTPRN20.73782139 0.34403344 0.62866877 rs12959952 18 46494835 intron MAPK40.7036857 0.19973021 0.68642326 rs10497208 2 160695167 intron ITGB61.09178513 0.75352212 0.73334585 rs496888 1 12155393 intron TNFRSF1B0.98849714 0.96835223 0.58209238 rs246394 5 149478344 intron PDGFRB1.07800003 0.8049839 0.63067265 rs3736395 5 75924224 intron IQGAP22.26291757 0.01047821 1.38697287 rs1573706 20 40354563 intron PTPRT1.49949889 0.19631716 1.6069948 rs17763453 17 3664884 intron C17orf851.84921488 0.0363718 1.89696314 rs1050382 17 59753732 locus-regionPECAM1 1.20359468 0.46433271 1.74401131 rs161042 5 146166067 intronPPP2R2B 1.3106124 0.45765546 0.38138725 rs1105238 1 159948285 intronFCRLA 1.75481239 0.04261883 1.35815008 rs11032349 11 33686248 mrna-utrCD59 0.42542725 0.07218081 0.55987429 rs7641625 3 37642638 intron ITGA91.47989139 0.19643664 1.63849578 rs3733678 5 149491985 intron PDGFRB1.75835283 0.22087157 2.06780589 rs13172280 5 35063668 intron AGXT21.38945614 0.21352732 1.73502557 rs7246376 19 8109328coding-nonsynonymous FBN3 1.47283872 0.22675894 1.68780469 rs704697 1133681356 mrna-utr CD59 0.81783308 0.4595754 0.64014021 rs2283539 1624036462 intron PRKCB1 1.42703837 0.20435086 1.67553526 rs926479 2040786436 intron PTPRT 0.85658553 0.82748284 2.59667403 rs12969613 1865710412 intron CD226 0.79877362 0.40429658 0.73759216 rs1007822 1865706201 intron CD226 0.79877362 0.40429658 0.73861498 rs161021 5146189300 intron PPP2R2B 1.40187743 0.35609199 0.36047838 rs832517 1293164318 intron PLXNC1 0.69066171 0.1907413 0.68112858 rs4955104 330696707 intron TGFBR2 1.79111758 0.0867806 1.70995826 rs6214 12101317699 mrna-utr IGF1 1.71901496 0.04522154 1.61292084 rs910682 6112282428 intron FYN 2.5624024 0.00382559 Inf rs7072398 10 6119852intron IL2RA 1.04244072 0.87305095 0.57726445 rs3828016 20 1865290intron SIRPA 0.50163574 0.01962402 0.70944458 rs13206518 6 6098001intron F13A1 0.80015969 0.688464 0.47126387 rs976881 1 12156341 intronTNFRSF1B 1.41934278 0.21707063 1.75339747 rs17201075 5 41221364 intronC6 1.09771229 0.86532931 3.71934504 rs1436522 4 87183196 intron MAPK100.89211758 0.75710477 0.61156718 rs7130876 11 48007571 intron PTPRJ1.54565632 0.15881083 0.52537558 rs6021183 20 49455556 intron NFATC21.44353751 0.29803193 2.90323676 rs6837303 4 111189034 locus-regionELOVL6 0.64314341 0.1435302 0.69472635 rs4798598 18 7805873 intron PTPRM0.65847522 0.12886739 0.69046153 rs7732671 5 149192436coding-nonsynonymous PPARGC1B 3.20354454 0.00589543 1.55843339 rs8052746 31773173 intron BAT5 0.55014299 0.06535639 0.62947384 rs6769530 3158512216 intron VEPH1 1.03295124 0.92248422 0.54286612 rs1519602 2196736037 intron STK17B 0.55320744 0.03324443 0.73904041 rs7559522 245903540 intron PRKCE 1.04566366 0.85817157 0.65154256 rs2575674 487156570 locus-region MAPK10 1.10853608 0.74215687 0.58503629 rs24409120 42664524 intron PKIG 1.80520247 0.09789911 1.75887237 rs11265416 1158738437 intron SLAMF6 2.35933243 0.37113726 0.21061583 rs7987909 1323106829 intron TNFRSF19 1.40983092 0.34867961 2.88724265 rs1797647 1212143345 mrna-utr BCL2L14 0.71062358 0.26179611 0.74897192 rs12034383 1205870218 intron CR1 1.23123613 0.39538637 1.48956715 rs169142 1624039431 intron PRKCB1 0.64831743 0.08571383 0.71324157 rs2296449 1117380273 intron IGSF2 0.29276092 0.25225893 0.47588685 rs793816 4185591486 intron IRF2 0.40984979 0.42558509 0.23730079 rs246395 5149479865 coding-synonymous PDGFRB 1.38582698 0.27133701 0.6194716rs246390 5 149476514 intron PDGFRB 0.7247334 0.2684215 0.72046124rs4955272 3 32288680 intron CMTM8 0.96089791 0.9051644 0.60948044rs6060855 20 29762606 intron BCL2L1 0.895837 0.81688231 0.43117643rs9831803 3 191844191 intron IL1RAP 1.34971585 0.38907767 1.59107034rs12506181 4 15576875 — — 0.74922786 0.35551237 0.6513769 rs4245886 332279107 intron CMTM8 0.75313095 0.34382198 0.73876461 rs244656 5133477726 locus-region TCF7 1.06335655 0.86197643 0.48971131 rs9817149 3191740949 intron IL1RAP 2.85058652 0.02464441 1.86248097 rs4472605 934556190 intron CNTFR 1.79149362 0.12460998 1.45596316 rs2595204 246047369 intron PRKCE 1.09030672 0.76799091 1.57921594 rs17317153 2040380498 intron PTPRT 1.32934137 0.42616821 2.63656846 rs4572808 332292718 intron CMTM8 1.31637632 0.32982957 1.32095634 rs2287768 5147471725 intron SPINK5 0.84607856 0.59736723 0.63187513 rs2227562 1075342967 intron PLAU 0.94723133 0.87839576 0.60790359 rs4094864 1865696478 intron CD226 0.88291236 0.63844854 0.71121514 rs831603 1133715214 — — 0.74543407 0.29031682 0.69047971 rs6850557 4 111130464intron EGF 1.28335256 0.38183122 0.61087182 rs6863088 5 179612366 intronMAPK9 0.664833 0.14196536 0.48692773 rs1041067 1 158723751 intron SLAMF62.2184953 0.01398437 0.43080195 rs17141840 6 6118369 intron F13A12.07470652 0.08885017 1.95408011 rs10406354 19 59022044 — — 0.899527420.77565299 0.52404025 rs6065460 20 40363108 intron PTPRT 0.421237280.0634589 0.65721731 rs12667537 7 157343101 intron PTPRN2 0.593054840.08714542 0.70517477 rs17811425 20 40856507 intron PTPRT 1.331481630.28994099 1.54496509 rs2302267 23 12795499 intron TLR7 1.816542230.03143813 1.4130263 rs4820059 22 30676468 intron YWHAH 0.815286390.47453164 1.72048152 rs6621980 23 104690227 intron IL1RAPL2 1.288827080.18109236 1.3068943 rs1007212 15 97101441 intron IGF1R 1.558693310.09640159 1.27530638 rs866484 1 157253101 coding-nonsynonymous IFI161.22252083 0.52829257 1.56924172 rs3181096 2 204278337 locus-region CD281.36261441 0.27972083 1.37728226 rs2302759 16 49385102 intron CYLD0.33689733 0.01461099 0.71273483 rs2275603 1 159948404coding-nonsynonymous FCRLA 1.64949637 0.07041442 1.33588972 rs5996577 2222251427 intron IGLL1 2.1220002 0.02489912 1.72345433 rs2076846 106103259 intron IL2RA 1.13945745 0.63633591 0.59088718 rs4639174 5179602877 intron MAPK9 1.42452019 0.30825037 2.34009523 rs17834679 1956961899 intron FPRL1 0.64573737 0.1415216 0.67581905 rs3024486 66090408 mrna-utr F13A1 1.9586438 0.27132607 8.87599881 rs2279590 827512170 intron CLU 0.92228597 0.76719657 1.75040285 rs9867325 3138101599 intron NCK1 1.62323973 0.10735731 1.51983072 rs2010452 337741319 intron ITGA9 1.46806911 0.17169416 1.54025474 rs12451415 1711947505 intron MAP2K4 0.30015344 0.00896293 0.74534892 rs4253655 2244947835 intron PPARA 2.32421494 0.01612296 1.54643399 rs6058391 2029743569 intron BCL2L1 0.96518672 0.94244112 0.44238887 rs7692976 4111131016 intron EGF 0.85015165 0.54038359 0.72312756 rs6482644 10129715311 intron PTPRE 0.72051209 0.23151259 0.76981675 rs9426315 129497962 intron PTPRU 2.25036285 0.00453832 1.3875101 rs2286414 7157167781 intron PTPRN2 3.20084147 0.02222804 3.78156695 rs6544865 246044534 intron PRKCE 1.27313525 0.40339922 1.76038942 rs1984399 2040312545 intron PTPRT 1.38508533 0.20837745 1.46992979 rs1838065 1054199263 intron MBL2 1.34748907 0.24834257 1.46857224 rs11214108 11111548824 locus-region TEX12 1.56594405 0.23747814 2.23726449 rs717176 415604412 intron PROM1 0.73755539 0.24483727 0.68663689 rs1797646 1212143028 intron BCL2L14 0.76049374 0.36369491 0.76117236 rs2238337 1589156736 intron BLM 1.7414468 0.03857242 1.50742576 rs763361 18 65682622coding-nonsynonymous CD226 1.07002722 0.79641874 1.45817642 rs4027402 1463566502 coding-nonsynonymous SYNE2 0.29027382 0.01182678 0.76414481rs970283 20 40713729 intron PTPRT 1.39292381 0.49302644 0.54068963rs4953292 2 46045487 intron PRKCE 0.61471861 0.06917241 0.71271184rs7541717 1 71179181 intron PTGER3 0.82329266 0.52082934 0.55588639rs1523474 3 188942191 intron BCL6 0.54023628 0.03951804 0.80092435rs4902264 14 63561448 coding-nonsynonymous SYNE2 0.31358432 0.013158741.91932441 rs210431 23 104831589 intron IL1RAPL2 1.23663197 0.260197421.25792622 rs6780432 3 106985186 intron CBLB 0.49699735 0.096901560.64739941 rs1058240 10 8156604 mrna-utr GATA3 0.81437984 0.574240390.60486059 rs2305340 12 7157242 — — 0.45089796 0.05819758 0.73801084rs6751395 2 46134145 intron PRKCE 1.10034772 0.70820629 0.55127786rs12881815 14 63674348 coding-nonsynonymous SYNE2 4.93816542 0.008742233.27810424 rs9991904 4 111142028 intron EGF 1.17849809 0.56911420.60057077 rs509749 1 159060184 coding-nonsynonymous LY9 1.666967780.05648367 1.38107099 rs1044141 7 43630805 coding-nonsynonymous STK17A1.35120379 0.34792227 1.54280229 rs878081 21 44532705 coding-synonymousAIRE 0.70507698 0.2927785 0.66315301 rs2227827 5 76054800 intron F2R1.51074004 0.49237438 2.20757565 rs11574113 12 46525167 intron VDR0.07642322 0.01288301 2.46E−161 rs17110948 5 149498698 intron PDGFRB0.76392252 0.61226492 0.49768788 rs1865462 7 157330723 intron PTPRN23.69492819 0.00687723 1.76884429 rs1552323 20 3398811 locus-region ATRN1.34848656 0.39325823 1.84726427 rs872071 6 356064 mrna-utr IRF40.59007603 0.05289113 0.68154856 rs11852361 15 89127103coding-nonsynonymous BLM 0.37852792 0.15612895 0.55754201 rs2288522 1960400287 intron PTPRH 1.67691064 0.16037886 1.65957717 rs10854166 1918513844 intron FKBP8 1.06807784 0.8007258 1.47150955 rs17419586 1323148712 locus-region TNFRSF19 0.97848495 0.93879471 1.8778521 rs807843917 11983357 intron MAP2K4 1.87710308 0.02841666 1.51384634 rs2569190 5139993100 intron CD14 1.39020846 0.216763 1.59274474 rs17748322 575911385 intron IQGAP2 2.2993276 0.00733668 1.14298838 rs17228097 337502408 intron ITGA9 1.58216805 0.19915925 1.37147549 rs10104302 857030794 intron LYN 1.36776903 0.32678276 1.44246121 rs17283264 346228570 — — 1.85735199 0.10142812 6.6280982 rs1062069 5 149412806locus-region CSF1R 1.23466277 0.57989157 1.92846985 rs1724120 2 96173058mrna-utr DUSP2 0.78255986 0.32792438 0.72325427 rs7647903 3 3108791intron IL5RA 2.13450415 0.01128258 1.23815585 rs11237451 11 77703107intron GAB2 0.65565062 0.20267608 0.73454025 rs10165797 2 113544921intron IL1F10 1.49689483 0.11969393 1.39321068 rs1206486 7 121339630intron PTPRZ1 1.34572269 0.26382119 1.49333138 rs706121 9 33250632intron BAG1 0.90288507 0.75541553 2.22530992 rs13042473 20 40843315intron PTPRT 0.59954867 0.16519214 0.7743799 rs3024498 1 205008152mrna-utr IL10 0.75456541 0.37841053 0.71982913 rs7289754 22 20926259 — —1.98404501 0.01102149 1.08058008 rs11168267 12 46537809 intron VDR0.29285052 0.05042848 0.01236529 rs1918309 12 93220659 intron PLXNC11.03323499 0.91214827 1.51539468 rs17671456 8 22441022 intron PPP3CC1.61060959 0.21643286 1.60308204 SNP HIGS P MIBS Odds MIBS P Meta OddsMeta P rs12368829 1.55E−07 0.970246771 0.98476165 0.25439022 1.81E−07rs4147385 0.00046696 1.162263286 0.77330466 2.43554195 1.08E−06rs11744216 1.44E−05 0.467690712 0.3787925 0.31650564 5.86E−06 rs175352134.45E−06 0.348814754 0.07743061 0.54098429 1.04E−05 rs100720560.00074227 0.311502349 0.00011672 0.57029367 1.05E−05 rs100548250.0001897 0.419079017 0.10365859 0.36525145 1.10E−05 rs12546235 9.63E−060.57082165 0.51527316 0.43960107 1.64E−05 rs2071336 5.19E−07 0.245243770.24041836 0.27143985 0.00010608 rs414634 0.00177128 1.0175305830.962581 1.72218627 0.00012352 rs17725712 0.01195522 3.3890067250.02382404 2.99952628 0.00012428 rs4242389 8.81E−06 0.8297663590.80181693 0.4994584 0.00012879 rs11773821 0.0008452 0.4686999940.10133446 0.50872671 0.00012997 rs8005905 0.0003978 0.8017708080.6502241 0.48106483 0.00013186 rs1863993 0.44319157 5.5809351560.00469048 4.32777987 0.00015861 rs9482888 NA 8.839576621 0.022215610.7547944 0.00018212 rs6476985 0.00536715 2.134496929 0.146057172.11637663 0.00027521 rs440238 0.04195541 0.689246147 0.337664730.59283279 0.00032172 rs2278324 0.00282462 0.758631103 0.619583971.87163184 0.00034725 rs3826392 0.0084676 0.569023823 0.119034290.60997937 0.00040366 rs12051769 0.00843671 0.602562032 0.180718930.61396868 0.00044857 rs1378796 0.00049546 0.777886845 0.55150470.58667166 0.00058411 rs6065467 0.00162751 0.844491824 0.779084310.57700459 0.00058673 rs3845422 0.00278781 0.765244738 0.527680760.59103311 0.00066496 rs208250 0.00614501 2.310452806 0.030152811.5640073 0.00072107 rs1884564 0.00016232 1.228896815 0.731178370.55576556 0.00076519 rs424051 0.08378924 0.672961838 0.308553760.61133786 0.00078465 rs2596606 0.00317447 0.789526971 0.583321571.80948675 0.00087248 rs9892152 0.00076293 1.389910702 0.350129171.55068941 0.00091287 rs12325842 0.01057338 0.655448359 0.28623990.61855994 0.00094923 rs3815003 0.00175443 0.837715833 0.655551390.6254446 0.0009581 rs390406 0.00011495 1.409500379 0.455434290.57751687 0.00096039 rs244090 0.00918138 1.655049937 0.251538271.78317553 0.00102069 rs1882019 0.00575273 0.413630679 0.095877920.5432514 0.00102399 rs2869460 0.0026252 0.915575879 0.816201580.6164075 0.00111423 rs2879097 0.00665552 0.974927042 0.953564490.63128529 0.00119921 rs244076 0.01007464 1.655049937 0.251538271.78255866 0.0012403 rs638251 0.00136003 0.665759136 0.279861950.66313286 0.00124552 rs11952962 0.14102305 2.654850747 0.040399541.76802039 0.0012525 rs10074391 0.01865724 4.556804728 0.012221772.44009991 0.00126698 rs7170919 0.00547374 0.734226073 0.47687090.62260685 0.00131742 rs11780679 0.02719962 0.325285615 0.052637280.46297251 0.00132003 rs4077341 0.00519201 0.507287168 0.139003960.64934295 0.00132538 rs12001295 0.05272256 3.889310136 0.022320572.30783236 0.00132646 rs1003854 0.00808487 0.567523116 0.162427010.62006744 0.00133582 rs246392 0.00056846 0.462869036 0.023569770.6541726 0.00137337 rs7690305 0.00290621 0.712582883 0.532370790.60144396 0.0014244 rs17652304 0.49335132 4.730242662 0.153719413.86360763 0.00146254 rs9313487 0.0034416 0.208542205 0.172175070.44575207 0.00150463 rs1457238 0.03083353 0.229441733 2.44E−050.67624734 0.00168974 rs12692566 0.00193067 0.81400343 0.695424631.80458897 0.00175191 rs3797390 0.35032961 2.263995603 0.034478041.60293238 0.00182055 rs2070783 0.00171067 1.439750782 0.27618111.51376522 0.00193313 rs1264456 0.00245695 1.371604918 0.463207060.67448283 0.00199097 rs1075846 0.01175816 0.502892078 0.04090320.67989373 0.00201972 rs6093584 0.1173883 0.475557176 0.039147290.64778754 0.00209511 rs13173943 0.00484349 1.135520315 0.740660771.58085124 0.00210867 rs10797666 0.00330048 0.881837867 0.750797110.63897389 0.00211897 rs4724231 0.00020324 1.144452734 0.874109850.52878863 0.00213939 rs613613 0.33851924 0.43635212 0.041512540.61461746 0.00219926 rs6742576 0.06345516 1.95184538 0.097067411.75133997 0.00220974 rs927335 0.01410875 1.631801224 0.214856611.5813765 0.00222182 rs1638006 0.00560578 0.672815037 0.333419490.65310735 0.00228823 rs12959952 0.05307649 0.496605859 0.02913220.64845801 0.00231721 rs10497208 0.04098183 0.229441733 2.44E−050.68428905 0.00232585 rs496888 0.00079136 0.72936899 0.459799490.66556634 0.0023772 rs246394 0.00452891 0.44036657 0.026174320.66714381 0.00243689 rs3736395 0.17646102 2.065974332 0.115697861.71358192 0.00246551 rs1573706 0.04833766 2.213076945 0.038781191.67701827 0.00247535 rs17763453 0.01033902 1.041064199 0.917611571.67503165 0.00254263 rs1050382 0.00167956 1.245746436 0.550316641.50011877 0.00265991 rs161042 2.05E−05 0.916673345 0.825847830.59559565 0.00272184 rs1105238 0.10163662 2.459090844 0.048420321.5518509 0.00275769 rs11032349 0.03097707 0.570364102 0.246182810.5323338 0.00276883 rs7641625 0.02261696 1.701486593 0.139730381.605386 0.0027894 rs3733678 0.02996296 2.914679958 0.0752997 2.091419940.00281082 rs13172280 0.0036724 1.135520315 0.74066077 1.532970460.00281937 rs7246376 0.01577555 2.116813201 0.16148837 1.661676080.00285523 rs704697 0.01375692 0.467296279 0.05636814 0.657328580.00291847 rs2283539 0.01026196 1.431999362 0.34269455 1.561206140.00297676 rs926479 0.07353594 9.982484611 0.00055812 2.890901190.00312637 rs12969613 0.05884827 0.37050971 0.00440838 0.684019860.00312925 rs1007822 0.05919215 0.37050971 0.00440838 0.684835470.00316234 rs161021 7.72E−06 1.075853393 0.86384871 0.595423870.00326861 rs832517 0.01733639 0.642026655 0.25481129 0.678566090.00327793 rs4955104 0.01159083 1.184086117 0.63734029 1.604269410.00333424 rs6214 0.0038546 0.629670784 0.25015386 1.477545 0.00337387rs910682 NA 1.614806551 0.38991522 2.2787084 0.00337616 rs70723980.00039605 0.856265088 0.66109688 0.69435573 0.00343648 rs38280160.04488799 0.800559925 0.50519681 0.67294756 0.00343895 rs132065180.02930569 0.089255123 0.00339299 0.44557584 0.0034403 rs9768810.00253158 0.932227215 0.86130551 1.52797732 0.00346769 rs172010750.00846313 3.329956454 0.03022541 2.45381211 0.00351449 rs14365220.00435674 0.707613566 0.27826946 0.66436007 0.00356592 rs71308760.00026877 0.357821168 0.05226772 0.65169287 0.0036519 rs60211830.0045594 1.925732512 0.28176322 1.99075048 0.00365776 rs68373030.03179239 0.626696378 0.1909502 0.67359438 0.00383111 rs47985980.01799934 0.76514178 0.467531 0.69192431 0.00391466 rs77326710.11260985 1.478295674 0.55400167 1.88287184 0.00401273 rs8052740.01306354 1.032014723 0.94369336 0.64720367 0.00420173 rs67695300.00098157 0.777886845 0.5515047 0.64910947 0.00426387 rs15196020.08236304 0.633695267 0.233687 0.67483508 0.00428548 rs75595220.00878969 0.509902099 0.02321788 0.70158138 0.00433721 rs25756740.00106201 0.755301384 0.40959324 0.683401 0.00434884 rs244091 0.02595141.412033578 0.42259279 1.69990307 0.0044037 rs11265416 NA 12.097708630.00276237 5.99409961 0.00441809 rs7987909 0.00560456 1.8191764470.23779462 1.9493235 0.00444665 rs1797647 0.09192002 0.3374767730.00654404 0.67165266 0.00445714 rs12034383 0.02330856 2.2033601650.05468089 1.46637086 0.00452342 rs169142 0.0696807 0.605725581 0.1548710.67605094 0.00452569 rs2296449 0.05303457 0.214111262 0.047148850.39451609 0.00452998 rs793816 0.00578488 18643042927 NA 0.261565340.00453749 rs246395 0.00236794 0.458094524 0.02696439 0.693386910.00467196 rs246390 0.07735733 0.569077489 0.04039748 0.68095860.00472586 rs4955272 0.00517256 0.569607579 0.18861383 0.660116810.00472636 rs6060855 0.00181195 0.732955751 0.60068371 0.540407860.00477793 rs9831803 0.07946045 3.921246215 0.00655085 1.729896260.00480705 rs12506181 0.02247829 0.57107144 0.13832885 0.658743230.00482864 rs4245886 0.05011435 0.469457936 0.030224 0.697610170.00483857 rs244656 0.00097469 0.669055839 0.45543166 0.611560580.00486188 rs9817149 0.15450723 4.730951503 0.20808618 2.379042150.00498185 rs4472605 0.05529258 2.135278739 0.11254484 1.582600360.00502758 rs2595204 0.00863162 1.64977881 0.14002211 1.467010470.00511685 rs17317153 0.00486086 1.800676856 0.27972342 1.880001090.00516092 rs4572808 0.0529861 2.310419141 0.02300502 1.402243520.00521911 rs2287768 0.02210027 0.504992842 0.06324674 0.650987070.00527658 rs2227562 0.02243608 0.39689553 0.02268151 0.624417210.00528067 rs4094864 0.03842952 0.409810295 0.01211854 0.695951110.0053456 rs831603 0.03075735 0.551646182 0.12308197 0.68387190.00536337 rs6850557 0.00404606 0.417295012 0.01518957 0.684925020.00541026 rs6863088 0.00026652 2.166432987 0.04781715 0.661132660.00542248 rs1041067 NA 1.823670971 0.17898745 2.07360552 0.0054606rs17141840 0.02115822 1.230686828 0.71387947 1.84994048 0.00546749rs10406354 0.00121281 1.088478107 0.87097154 0.62946059 0.00548652rs6065460 0.05626947 0.587645404 0.24739883 0.60311188 0.00559256rs12667537 0.02875229 0.789227493 0.56782914 0.69015028 0.00562835rs17811425 0.01789273 1.428769234 0.28635744 1.46627399 0.00567987rs2302267 0.30851561 1.748933254 0.12694004 1.66927173 0.00569168rs4820059 0.00287257 2.658471404 0.02367452 1.49145813 0.00571302rs6621980 0.04939986 1.409589457 0.15015776 1.31936028 0.00575959rs1007212 0.16726864 2.729934463 0.01579015 1.46480877 0.00588403rs866484 0.06374432 4.219859274 0.00436883 1.64336082 0.00591764rs3181096 0.1075962 1.84576278 0.03149599 1.47683865 0.00593852rs2302759 0.10011032 0.580423115 0.2796878 0.6191119 0.00621838rs2275603 0.12468672 2.311760859 0.07374143 1.49849868 0.00623442rs5996577 0.02398456 0.515875154 0.32068033 1.67156256 0.00624054rs2076846 0.00126669 0.648216671 0.298268 0.69490504 0.00626233rs4639174 0.00444984 1.174127844 0.78806174 1.78382912 0.00628683rs17834679 0.02521038 0.789642141 0.47013849 0.68786418 0.00631208rs3024486 0.01728117 3.091031331 0.11776871 3.10843837 0.00636386rs2279590 0.00106384 1.351465322 0.44422561 1.44792048 0.00651877rs9867325 0.04684429 1.450965731 0.34480767 1.53618707 0.00659895rs2010452 0.04867542 1.797560506 0.18486799 1.54750999 0.00666053rs12451415 0.12088012 0.602191129 0.22225372 0.64537547 0.00668182rs4253655 0.0722436 1.127438262 0.78892856 1.63851165 0.00672637rs6058391 0.00238366 0.732955751 0.60068371 0.55342866 0.00688493rs7692976 0.05480184 0.391594532 0.01297711 0.69784007 0.00692522rs6482644 0.24768847 0.305341161 0.0030658 0.64947734 0.00697574rs9426315 0.06850014 0.886855435 0.74404124 1.46103026 0.00701027rs2286414 0.05552253 0.574738926 0.65899547 2.85777667 0.00711592rs6544865 0.0075062 1.277095333 0.48285441 1.51025069 0.00715909rs1984399 0.0342318 1.461046463 0.27809817 1.44433829 0.00726788rs1838065 0.03270155 1.464967692 0.24263104 1.43409468 0.00737466rs11214108 0.01288866 1.417426141 0.58443051 1.85014939 0.00742465rs717176 0.0188805 0.787432901 0.50995334 0.7104371 0.00748396 rs17976460.11066569 0.337476773 0.00654404 0.68924202 0.00760094 rs22383370.01187583 0.690759416 0.3183848 1.4161782 0.00764643 rs7633610.02843145 2.139825301 0.02812813 1.42502266 0.00770211 rs4027402 NA0.506797492 0.25934214 0.36264054 0.00772918 rs970283 0.004450510.275876819 0.09376977 0.60133443 0.00779681 rs4953292 0.061810180.778632189 0.42203158 0.69784319 0.00782152 rs7541717 0.002694271.038205399 0.93208105 0.66420876 0.00787324 rs1523474 0.239788750.499496867 0.06316575 0.67718014 0.00793313 rs4902264 NA 0.5067974920.25934214 0.37561345 0.00804314 rs210431 0.06991452 1.528598810.08095319 1.29134824 0.00805292 rs6780432 0.02470974 0.8868095640.7963535 0.64673151 0.00808053 rs1058240 0.0255244 0.4296761570.09398897 0.62224421 0.0080995 rs2305340 0.12689838 0.4922426690.10309747 0.64405121 0.00812478 rs6751395 0.00034599 0.9694636030.93275275 0.70858004 0.00823818 rs12881815 0.07772938 0.2962398260.34610186 3.08321144 0.00825819 rs9991904 0.00245033 0.6521637560.20495758 0.70286829 0.00826286 rs509749 0.05996023 1.2434359960.59863126 1.43368631 0.00828454 rs1044141 0.05186795 1.9669175590.09285948 1.55179894 0.00837565 rs878081 0.0286662 0.6751500830.29845254 0.67339544 0.00838392 rs2227827 0.26149332 12.484447080.00172115 2.85293367 0.00839616 rs11574113 NA 0.354546359 0.13099250.22168005 0.0084421 rs17110948 0.01809374 0.456298626 0.197906080.53511478 0.00850426 rs1865462 0.26604918 1.166206662 0.881142812.40061042 0.00851779 rs1552323 0.02747993 1.980703511 0.162456361.68803574 0.00853525 rs872071 0.01543522 1.240225714 0.534645070.71596244 0.00867939 rs11852361 0.05155452 0.197387295 0.155032890.49653661 0.00879554 rs2288522 0.06950403 1.877809135 0.200304191.7000779 0.00883537 rs10854166 0.03416572 1.991587477 0.030987421.42534666 0.00884885 rs17419586 0.00291577 1.623563578 0.234557321.50606072 0.00891196 rs8078439 0.04810873 0.987701372 0.973467441.49666589 0.00892432 rs2569190 0.00646771 0.863159962 0.690900861.41990798 0.00895345 rs17748322 0.50840081 2.283820346 0.04776141.50698683 0.00897021 rs17228097 0.1563137 2.712132468 0.024632771.57527645 0.00899615 rs10104302 0.04726518 2.153080222 0.10518111.48498599 0.00903621 rs17283264 0.00148629 0.670047968 0.581882862.14058282 0.00919713 rs1062069 0.04672765 4.424252439 0.019042351.82622304 0.00948614 rs1724120 0.06606352 0.512380618 0.067726270.70630159 0.00954347 rs7647903 0.28448998 2.528852728 0.14396321.51632475 0.00955962 rs11237451 0.06356768 0.439096926 0.106963140.69088709 0.0095633 rs10165797 0.04788534 1.256490192 0.450719991.39187312 0.00958124 rs1206486 0.03825241 1.837816069 0.222901121.47214103 0.00958255 rs706121 0.00133522 1.557420871 0.290477531.59146367 0.00958826 rs13042473 0.25507792 0.386478551 0.015441640.64042143 0.00972508 rs3024498 0.06700756 0.191015467 0.009715690.67509588 0.00975546 rs7289754 0.67991022 2.249557811 0.01963011.4390963 0.00976474 rs11168267 NA 0.262332634 0.09134851 0.280686630.0098283 rs1918309 0.01258535 1.527641748 0.18439689 1.406155310.00991575 rs17671456 0.06629775 2.213446139 0.15422973 1.672869650.00996644

1-83. (canceled)
 84. A microarray for predicting the risk of developingantibodies against Factor VIII (FVIII) in an individual diagnosed withHemophilia A, the microarray comprising a support having a plurality ofdiscrete regions, each discrete region having a nucleic acid fragmentspotted thereon, wherein at least 10 nucleic acid fragments spotted onthe support comprise a sequence that is complementary to a genomicsequence that flanks a single nucleotide polymorphism (SNP) selectedfrom the group consisting of a SNP listed in Table 1, a SNP listed inTable 2, a SNP listed in Table 3, and a SNP listed in Table
 4. 85-88.(canceled)
 89. A method for predicting the risk of developing antibodiesagainst Factor VIII (FVIII) in an individual diagnosed with HemophiliaA, the method comprising the steps of: (a) detecting the identity of thenucleotide corresponding to the genomic position of at least 10 singlenucleotide polymorphisms (SNPs) selected from the group consisting of aSNP listed in Table 1, a SNP listed in Table 2, a SNP listed in Table 3,and a SNP listed in Table 4, in a biological sample from the individual;and (b) predicting the risk of the individual of developing antibodiesto FVIII, wherein the detection of a SNP associated with an odds ratioof less than 1 is predictive of a decreased risk of developingantibodies against FVIII and the detection of a SNP associated with anodds ratio of more than 1.0 is predictive of an increased risk ofdeveloping antibodies against FVIII.
 90. The method of claim 89, whereinthe method further comprises a step of: (c) assigning a treatmentcomprising administration of Factor VIII to an individual with apredicted decreased risk of developing antibodies against Factor VIII.91. The method of claim 89, wherein the method further comprises a stepof: (c) administering Factor VIII to an individual with a predicteddecreased risk of developing antibodies against Factor VIII.
 92. Themethod of claim 89, wherein the method further comprises a step of: (c)assigning a treatment comprising administration of Factor VIII bypasstherapy to an individual with a predicted increased risk of developingantibodies against Factor VIII.
 93. The method of claim 89, wherein themethod further comprises a step of: (c) administering Factor VIII bypasstherapy to an individual with a predicted increased risk of developingantibodies against Factor VIII.
 94. The method of claim 89, wherein atleast one of the nucleotides detected corresponds to the genomicposition of a SNP selected from the group consisting of rs12368829,rs11744216, rs1863993, rs4147385, rs12546235, rs4242389, rs10054825,rs17535213, rs10072056, and rs17725712.
 95. The method of claim 94,wherein the presence of any one of SNPs rs12368829, rs11744216,rs12546235, rs4242389, rs10054825, rs17535213, and rs10072056 ispredictive of a decreased risk of developing antibodies against FactorVIII.
 96. The method of claim 95, wherein the method further comprisesthe step of: (c) assigning a treatment comprising administration ofFactor VIII to an individual having a SNP selected from the groupconsisting of SNPs rs12368829, rs11744216, rs12546235, rs4242389,rs10054825, rs17535213, and rs10072056.
 97. The method of claim 95,wherein the method further comprises the step of: (c) administeringFactor VIII to an individual having a SNP selected from the groupconsisting of SNPs rs12368829, rs11744216, rs12546235, rs4242389,rs10054825, rs17535213, and rs10072056.
 98. The method of claim 94,wherein the presence of any one of SNPs rs1863993, rs4147385, andrs17725712 is predictive of an increased risk of developing antibodiesagainst Factor VIII.
 99. The method of claim 98, wherein the methodfurther comprises the step of: (c) assigning a treatment comprisingadministration of Factor VIII bypass therapy to an individual having aSNP selected from the group consisting of rs1863993, rs4147385, andrs17725712.
 100. The method of claim 98, wherein the method furthercomprises the step of: (c) administering Factor VIII bypass therapy toan individual having a SNP selected from the group consisting ofrs1863993, rs4147385, and rs17725712.
 101. The method of claim 89,wherein the nucleotides detected correspond to the genomic position ofat least SNPs rs12368829, rs11744216, rs1863993, rs4147385, rs12546235,rs4242389, rs10054825, rs17535213, rs10072056, and rs17725712.
 102. Themethod of claim 101, wherein the presence of any one of SNPs rs12368829,rs11744216, rs12546235, rs4242389, rs10054825, rs17535213, andrs10072056 is predictive of a decreased risk of developing antibodiesagainst Factor VIII.
 103. The method of claim 102, wherein the methodfurther comprises the step of: (c) assigning a treatment comprisingadministration of Factor VIII to an individual having a SNP selectedfrom the group consisting of SNPs rs12368829, rs11744216, rs12546235,rs4242389, rs10054825, rs17535213, and rs10072056.
 104. The method ofclaim 102, wherein the method further comprises the step of: (c)administering Factor VIII to an individual having a SNP selected fromthe group consisting of SNPs rs12368829, rs11744216, rs12546235,rs4242389, rs10054825, rs17535213, and rs10072056.
 105. The method ofclaim 101, wherein the presence of any one of SNPs rs1863993, rs4147385,and rs17725712 is predictive of an increased risk of developingantibodies against Factor VIII.
 106. The method of claim 105, whereinthe method further comprises the step of: (c) assigning a treatmentcomprising administration of Factor VIII bypass therapy to an individualhaving a SNP selected from the group consisting of rs1863993, rs4147385,and rs17725712.
 107. The method of claim 105, wherein the method furthercomprises the step of: (c) administering Factor VIII bypass therapy toan individual having a SNP selected from the group consisting ofrs1863993, rs4147385, and rs17725712.